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First published online August 31, 2007
Journal of Experimental Biology 210, 3301-3310 (2007)
Published by The Company of Biologists 2007
doi: 10.1242/jeb.006106
Ventilatory and cardiovascular actions of centrally administered trout tachykinins in the unanesthetized trout
1 Laboratoire de Traitement de l'Information Médicale, INSERM U650,
and Laboratoire de Neurophysiologie, Faculté de Médecine et des
Sciences de la Santé, Université de Bretagne Occidentale, 22
avenue Camille Desmoulins, CS 93837, 29238 Brest Cedex 3, France
2 Department of Biochemistry, Faculty of Medicine and Health Sciences,
United Arab Emirates University, 17666 Al Ain, United Arab Emirates
* Author for correspondence (e-mail: jean-claude.lemevel{at}univ-brest.fr)
Accepted 17 July 2007
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), substance P (SP) and neurokinin A (NKA)
(5–250 pmol) on ventilatory and cardiovascular parameters in the
unanesthetized rainbow trout Oncorhynchus mykiss.
Intracerebroventricular (ICV) injection of NP evoked a dose-dependent
elevation of the ventilation rate (fV) but a reduction of
the ventilation amplitude (VAMP) that was caused by a
reduction of the magnitude of the adduction phase of the ventilatory signal.
The net effect of NP was to produce an hypoventilatory response since
the total ventilation (VTOT) was significantly reduced.
The minimum effective dose for a significant effect of NP on
fV and VAMP was 50 pmol. SP evoked a
significant elevation of fV, a concomitant depression of
VAMP, and a resultant decrease in VTOT
but only at the highest dose (250 pmol). NKA was without action on
fV but significantly decreased VAMP at
only the highest dose tested. In this case also, the net effect of NKA was to
reduce VTOT. When injected centrally, none of the three
peptides, at any dose tested, produced changes in heart rate or mean dorsal
aortic blood pressure (PDA). Intra-arterial injection of
the three tachykinins (250 pmol) produced a significant (P<0.05)
increase in PDA, but only SP and NKA induced concomitant
bradycardia. None of the three peptides produced any change in
fV or VAMP. In conclusion, our results
demonstrate that centrally injected tachykinins, particularly NP,
produce a strong hypoventilatory response in a teleost fish and so suggest
that endogenous tachykinins may be differentially implicated in
neuroregulatory control of ventilation.
Key words: neuropeptide , substance P, neurokinin A, ventilatory control, intracerebroventricular injection, teleost
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) and neuropeptide K (NPK)
are encoded by the single copy preprotachykinin A gene. Neurokinin B
is derived from the preprotachykinin B gene while the
preprotachykinin C gene encodes three peptides (hemokinin 1,
endokinin C and endokinin D), with limited structural similarity with SP (see
Conlon, 2004
). The tachykinins
exert their actions by binding to G-protein coupled receptors that are widely
distributed within vascular, endocrine and nervous tissues. SP is the
preferential agonist of the NK-1 receptor; NKA along with NP and NPK
are regarded as endogenous ligands of the NK-2 receptor; and NKB is the
preferred agonists of the NK-3 receptor
(Patacchini and Maggi, 2004).
In mammals, there is strong evidence for the importance of central nervous
system (CNS) tachykinins in the control of respiration
(Kumar and Prabhakar, 2003).
Micro-injection or bath application of SP into the pre-Bötzinger complex,
the primary source of rhythmogenesis situated in the reticular formation
(Smith et al., 1991),
increased respiratory frequency through an action on the NK-1 receptor
(Monteau et al., 1996;
Gray et al., 1999;
Gray et al., 2001).
Furthermore, NKA, NKB and agonists selective for NK-2 and NK-3 receptors
reduced respiratory frequency but increased tidal volume after injection
within the nucleus tractus solitarius (NTS)
(Mazzone and Geraghty, 2000).
In addition, central tachykinins are involved in cardiovascular regulation,
neuroendocrine secretion, pain transmission, and in certain behavioral
responses (see Satake and Kawada,
2006). In the periphery, the presence of tachykinins and their
receptors in lung indicate an important physiological role in local regulation
of the pulmonary system (see Meini and
Lecci, 2006), and tachykinins acting as neurotransmitters and/or
neuromodulators are implicated in regulation of cardiovascular and
gastrointestinal functions and inflammatory and immune processes (see
Holzer, 2006;
Page, 2006;
Walsh and McWilliams,
2006).
Orthologs of the mammalian tachykinins have been isolated and structurally
characterized in a wide range of tetrapod and non-tetrapod species (see
Conlon, 2004). In particular,
SP (Jensen and Conlon, 1992),
NKA (Jensen and Conlon, 1992)
and NP (Jensen et al.,
1993) have been purified from tissues of the rainbow trout
Oncorhynchus mykiss. In the unanesthetized trout, trout SP and trout
NKA given intra-arterially were equally effective in increasing both systemic
and coeliac resistance, leading to hypertension, bradycardia and a decrease in
cardiac output (Kagstrom et al.,
1996). These peptides were also approximately equipotent in
increasing the trout dorsal aortic vascular resistance in an in vitro
perfusion system (Kagstrom et al.,
1996). In contrast, trout SP was more potent than NKA in
stimulating the motility of the isolated trout intestinal smooth muscle and
the vascularly perfused trout stomach
(Jensen et al., 1993).
Neuroanatomical studies have revealed the presence of tachykinin-like
immunoreactivity in neuronal cell bodies and fibers throughout the brain of
several teleost fish, including the trout
(Vecino et al., 1989;
Batten et al., 1990;
Holmqvist and Ekstrom, 1991;
Moons et al., 1992), together
with high density of tachykinin binding sites
(Moons et al., 1992) but
central actions of tachykinins in fish are unknown. Rhythmic ventilatory
movements in fish are generated by a diffuse central pattern generator (CPG),
probably located within the reticular formation (see
Taylor et al., 1999), whose
activity is modulated by inputs originating from higher brain centers
(Shelton, 1959). Because of
the crucial role of central tachykinins in the control of respiratory
rhythmogenesis in mammals and the presence of a central tachykinergic system
in teleost fish, we propose the hypothesis that tachykinins in fish might be
involved in the central control of ventilation. Consequently, the present
study was carried out to investigate the effects of intracerebroventricular
(ICV) administration of synthetic replicates of trout NP, SP and NKA on
ventilation rate (fV), ventilation amplitude
(VAMP), dorsal aortic blood pressure
(PDA) and heart rate (fH) in the
unanesthetized rainbow trout. The central actions of the peptides on these
parameters were compared with their effects after intra-arterial (IA)
administration.
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(SSANPQITHKRHKINSFVGLM.NH2) were supplied in crude form
by GL Biochem Ltd (Shanghai, China) and purified to near homogeneity by
reversed-phase high-pressure liquid chromatography (HPLC) on a (2.2x25
cm) Vydac 218TP1022 (C-18) column (Separations Group, Hesperia, CA, USA). The
purity of all peptides tested was >98% and their identities were confirmed
by electrospray mass spectrometry. Peptides were firstly dissolved in 0.1% v/v
acetic acid and aliquots were stored at –25°C. For injections, the
peptides were freshly diluted to the desired concentration with Ringer's
solution (composition in mmol l–1: NaCl 124, KCl 3,
CaCl2 0.75, MgSO4 1.30, KH2PO4
1.24, NaHCO3 12, glucose 10 (pH 7.8) immediately prior to use.
Vehicle was made from Ringer solution containing an appropriate concentration
of acetic acid. All solutions were sterilized by filtration through 0.22 µm
filters (Millipore, Molsheim, France) before injection.
Animals
Adult rainbow trout (body mass 276±2 g; mean ± s.e.m.,
N=70) of both sexes were purchased locally and transferred in a
well-oxygenated and thermostatically controlled water tank to the laboratory.
All the fish were kept in a 1000-liter tank containing circulating
dechlorinated, aerated tapwater (11–12°C), under a standard
photoperiod (lights on 09:00 h–20:00 h). The fish were allowed at least
3 weeks to acclimate under these conditions before the experiments were
started. Experimental protocols were approved by the Regional Ethics Committee
in Animal Experiments, Brittany, France.
Experimental procedures
All surgical procedures were made under tricaine methane sulfonate
(3-amino-benzoic acid ethyl ester; 60 mg l–1 in tapwater
buffered with NaHCO3 to pH 7.3–7.5) anesthesia. The
techniques used for placement of the electrocardiographic (ECG) electrodes,
placement of the buccal catheter, cannulation of the dorsal aorta and
insertion of the ICV microguide have previously been described in detail
(Le Mével et al., 1993;
Lancien et al., 2004).
Briefly, two ECG AgCl electrodes (Comepa, 93541 Bagnolet, France) were
subcutaneously implanted ventrally and longitudinally at the level of the
pectoral fins. The incision was sutured across the electrodes and the leads
were sutured to the skin. The dorsal aorta was cannulated with a PE-50
catheter (Clay Adams, Le Pont De Claix, France). A flared cannula (PE-160) was
inserted into a hole drilled between the nares such that its flared end was
resting against the roof of the mouth. This cannula was used to record any
changes in buccal ventilatory pressure
(Holeton and Randall, 1967).
The absence of a neocortex in fish allowed the accurate placement of the ICV
microguide under stereomicroscopic guidance. A 25-gauge needle fitted with a
PE-10 polyethylene catheter was inserted between the two habenular ganglia and
descended into the third ventricle until its tip lay between the two preoptic
nuclei. An obturator was placed at the end of the PE-10 tubing and the cranial
surface was covered with hemostatic tissue followed by light quick-curing
resin. After surgery, the animals were force-ventilated with dechlorinated
tapwater and, following recovery of opercular movements, were transferred to a
6-liter blackened chamber supplied with dechlorinated and aerated tapwater
(10–11°C) that was both re-circulating and through-flowing. Oxygen
pressure within the water tank (PwO2) and pH were
continuously recorded and maintained at constant levels
(PwO2: 20 kPa; pH 7.4–7.6). A small horizontal
aperture was made along the upper edge of the chamber in order to connect the
ECG leads to an amplifier and to connect the dorsal aorta and the buccal
cannula to pressure transducers. This aperture permitted ICV injections of
peptides without disturbing the trout.
The trout were allowed to recover from surgery and to become accustomed to their new environment for 48–72 h. Each day, the general condition of the animals was assessed by observing their behavior, checking the ventilatory and the cardiovascular variables, and measuring their hematocrit. Animals that did not appear healthy, according to the range of values detailed in our previous studies, were discarded. After fV, VAMP, PDA and fH were maintained stable for at least 90 min, parameters were recorded for 30 min without any manipulation or ICV injection in control experiments.
Intracerebroventricular administration of tachykinins
The injector was introduced within the ICV guide prior to the beginning of
a recording session, which lasted 30 min. All injections were made at the
fifth min of the test but the injector was left in place for a further 5 min
to allow for complete diffusion of the agent and to minimize the spread of
substances upwards in the cannula tract. The fish received an ICV injection of
vehicle (0.5 µl) and 30 min later, an ICV injection of trout NP (5,
25, 50 and 100 pmol in 0.5 µl), SP or NKA (50, 100 and 250 pmol in 0.5
µl). The animals received a single ICV injection of one dose of peptide per
day. No single fish was studied for more than 2 days and control experiments
revealed that there was no significant change in performance over this period.
Pilot experiments showed that the initial ICV injection of vehicle had no
effect on the subsequent ICV injection of peptide. Furthermore, the
possibility of time-dependent changes in the measured variables was evaluated
by performing two sequential ICV injections of vehicle 30 min apart. There
were no significant changes in the recorded variables following the second
injection of vehicle compared to the changes observed after the first one.
Intraarterial administration of tachykinins
5 min after the beginning of the recording session, 50 µl of vehicle, or
trout tachykinins at an appropriate concentration, were injected through the
dorsal aorta and immediately flushed by 150 µl of vehicle. NP, SP
and NKA were tested at doses of 50, 100 and 250 pmol.
Data acquisition and analysis of the ventilatory and the cardiovascular variables
The ECG electrodes were connected to a differential amplifier (band pass:
5–50 Hz; Bioelectric amplifier, Gould & Nicolet, 91942 Courtaboeuf,
France) and a stainless steel bar was immersed in the water of the tank to act
as a reference electrode. The aortic cannula and the buccal catheter were
connected to P23XL pressure transducers (band-pass: 0–15 Hz; Gould &
Nicolet). These pressure transducers were calibrated each day using a static
water column. At the beginning of the experiments, the zero-buccal pressure
level was set electronically. The output signals from the devices were
digitalized at 500 Hz (PCI-1200 board, National Instruments, Austin, TX, USA)
during the 30 min recording period and the data were stored on a disc. The
time-series related to the ventilatory, the pulsatile PDA
and the ECG signals were processed off-line with custom-made programs written
in LabView 6.1 (Laboratory Virtual Instrument Engineering Workbench, National
Instruments). The ventilatory parameters were calculated as previously
described (Lancien et al.,
2004). Segments free of any movement artifacts on the ventilatory
signal were selected and fV (breaths
min–1) and the VAMP (arbitrary units,
a.u.) were determined. The fV was calculated from the
first harmonic of the power spectrum of the ventilatory signal using the fast
Fourier transformation. VAMP was calculated from the
difference between the maximal abduction phase and the maximal adduction phase
for each of the ventilatory movements. The net effect of the changes in
fV and VAMP on ventilation was
determined according to the formula
VTOT=fVxVAMP,
where VTOT is total ventilation. The overall ventilatory
response is determined by the combined output of the fV
and ventilatory stroke volume. By using only buccal pressure, we used an
indirect technique to estimate ventilatory water flow since
VAMP is not necessarily proportional to the ventilatory
stroke volume. However, this technique has the advantage of necessitating only
minimal surgery and is widely used in cardiorespiratory studies on fish
(Fritsche and Nilsson, 1993).
The mean PDA (kPa) was calculated from the pulsatile
PDA as the arithmetic mean of the systolic blood pressure
and the diastolic blood pressure, and the mean fH (beats
min–1) was determined from the ECG signal. All calculations
for fV, VAMP,
VTOT, PDA and fH
were made for the pre-injection period (0–5 min) and for five
post-injection periods of 5 min for each trout and the results were averaged
for trout subjected to the same protocol.
Statistical analysis
Data are expressed as means ± s.e.m. or + s.e.m. for each 5 min
period. In the figures and text, data refer to absolute values
(fV in breaths min–1;
VAMP in a.u.; VTOT in a.u.;
PDA in kPa; fH in beats
min–1) or maximal changes from baseline (pre-injection)
values. The data were analyzed using two-way ANOVA followed by the Bonferroni
post hoc test for comparisons between groups. Within each group, when
the overall preceding ANOVA analyses demonstrated statistically significant
differences, Dunnett's test was used for comparisons of post-injection values
with pre-injection values. The criterion for statistical difference between
groups was P<0.05. The statistical tests were performed using
GraphPad Prism 3.0 (GraphPad, San Diego, CA, USA).
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(Fig. 1B).
Comparing the vehicle-treated and NP-injected trout, NP caused
an impressive reduction in VAMP by decreasing in the
magnitude of the adduction phase of the lower jaw, i.e. by reducing the mouth
closing phase of the ventilatory cycle. Concurrently, NP caused a
potent elevation of fV. However, NP was without
effect on either PDA or fH.
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are summarized in
Fig. 2. Since 5 pmol NP
was without action on any parameters, these data are omitted from
Fig. 2.
Table 1 shows the maximal
changes in the ventilatory variables. There was no statistically significant
difference between the baseline values of the ventilatory and the
cardiovascular variables recorded during the control period and during the
pre-injection period prior to ICV injection of vehicle (data not shown). The
ICV injection of vehicle produced no significant change in the ventilatory and
in the cardiovascular parameters compared to pre-injection values
(Fig. 2,
Table 1). Compared with ICV
injection of vehicle, NP evoked a gradual dose-dependent elevation of
fV (Fig.
2A, Table 1) but a
progressive dose-dependent reduction of VAMP
(Fig. 2B and
Table 1). The net effect of the
peptide was a hypoventilatory response involving a significant dose-dependent
decrease in VTOT (Fig.
2C, Table 1).
NP at a dose of 25 pmol evoked a progressive elevation of
fV, reaching significance 25 min after injection, without
significant change in VAMP and VTOT.
The threshold dose for an effect of NP on both fV,
VAMP and VTOT was 50 pmol and this was
observed 15 min after the injection of the peptide
(Fig. 1A–C,
Table 1). At the maximum dose
of NP tested (100 pmol), a significant increase in
fV but reduction in VAMP and
VTOT occurred 10 min after ICV injection. In two trout out
of ten, the ICV injection of 100 pmol NP was followed by a dramatic
reduction in VAMP to near the noise level of the recording
system for periods of 10 to 20 s, giving the appearance of an apneic response.
During this phase, the inferior jaw of the trout remained largely abducted. No
fV could be accurately determined and results from these
two trout were not included within the data set. All actions of NP on
the ventilatory variables were of long duration since, after reaching their
peak value, parameters did not return to baseline values by the end of the
recording period. During the period in which NP produced marked changes
in fV and VAMP, there was no
significant change either in mean PDA
(Fig. 2D) or in
fH (Fig.
2E).
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As shown in Fig. 3, IA
injections of NP at doses of 50–250 pmol produced no change in
either fV, VAMP or
VTOT (Fig.
3A–C). However, NP (250 pmol) caused a significant
increase in mean PDA
(Fig. 3D). During this
hypertensive response there was no change in fH
(Fig. 3E).
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(Fig. 2), the effects of SP
were not dose dependent and only the highest dose of SP (250 pmol) produced a
significant elevation of fV
(Fig. 4A,
Table 1), a significant
reduction of VAMP (Fig.
4B, Table 1) and a
resultant significant decrease of VTOT
(Fig. 4C and
Table 1). The changes in these
parameters reached significance 10–15 min after ICV injection. No
significant change occurred in either PDA or
fH following the ICV injection of SP
(Fig. 4D,E). IA injection of SP caused no change in the ventilatory variables (not shown) and only the injection of 250 pmol SP produced a significant increase in mean PDA together with a fall in fH (PDA: +0.63±0.14 kPa; fH:–5.38±1.15 beats min–1). These changes were transient, reaching their maximal value 5 min after injection and returning to basal level 15 min after injection (not shown).
Ventilatory and cardiovascular responses to central and peripheral NKA
The results obtained following ICV injections of graded doses (50–250
pmol) of NKA are shown in Fig.
5. As with SP, the effect of NKA on the ventilatory variables
(Fig. 5A–C) was
relatively minor, with only the highest dose (250 pmol) producing a
significant decrease in VAMP
(Fig. 5B and
Table 1) and an overall
significant fall in VTOT
(Fig. 5C). This action of NKA
was of short duration with VAMP returning rapidly to
baseline values. No significant changes in mean PDA
(Fig. 5D) or
fH (Fig.
5E) were observed following ICV injection of NKA.
No change in fV and VAMP or in the cardiovascular variables was observed following the IA injections of 50 pmol NKA (not shown). The highest dose of NKA (250 pmol) was also without effect on the ventilatory variables but this dose NKA produced a slight but significant increase in mean PDA (+0.29±0.04 kPa) and a concomitant significant fall in fH (–3.16±0.50 beats min–1) 5 min after injection (not shown).
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on ventilation and demonstrates that ICV administration of
the native tachykinins NP, SP and NKA differentially affect ventilatory
movements in the unanesthetized trout. We provide evidence that the three
tachykinins tested have a differential action on the neuronal substrate
involved in respiratory rhythmogenesis. Since none of the peptides, at any
dose tested, produced substantial changes in either PDA or
fH, a strong argument is presented that observed changes
in the ventilatory pattern were not secondary to cardiovascular changes.
Furthermore, since the IA administration of the tachykinins did not affect
fV or VAMP at any dose tested, the
response observed following ICV injection clearly originated from the CNS
rather than from diffusion of the peptides to the periphery. The data indicate
that NP was about fivefold more potent than SP and NKA in producing an
elevation of fV, a reduction of VAMP,
and an overall hypoventilatory response. The N-terminal extension to the NKA
sequence in NP is not considered to be involved in receptor interaction
(see Conlon, 2004) so that the
increased potency of NP is probably a consequence of its increased
stability within the third ventricle relative to NKA and SP.
The distribution of tachykinin receptors in the trout brain has not been
reported but in another teleost species, the sea bass Dicentrarchus
labra, tachykinin-binding sites are located in various brain regions
including the entire hypothalamus and the medulla oblongata
(Moons et al., 1992). However,
the pharmacological properties of tachykinin receptors in fish have been
studied much less extensively than in mammals. In the unanesthetized rat,
NP evoked dose-dependent increases in mean arterial blood pressure and
fH, and produced behavioral responses that were attenuated
by the NK2-receptor antagonist SR48968. The NK1-receptor antagonist RP67580
was without effect, indicating that central actions of NP are mediated,
at least in part, through interaction with NK2-receptors
(Picard and Couture, 1996). In
mammals, the pre-Bötzinger complex is considered to be the primary source
of respiratory rhythmogenesis (Smith et
al., 1991) and micro-injection or bath application of SP into the
pre-Bötzinger complex increased respiratory frequency
(Monteau et al., 1996;
Gray et al., 1999). The effect
of SP was mediated by the NK-1 receptor
(Gray et al., 2001). The
central action of other mammalian tachykinins have not been studied so
extensively but in the anesthetized rat, NKA, NKB and agonists selective for
NK-2 and NK-3 receptors reduced respiratory frequency but increased tidal
volume after injection within the NTS
(Mazzone and Geraghty, 2000).
Further studies are required to determine whether the central action of
NP on ventilatory variables in trout involves interaction with a
receptor that resembles the mammalian NK-2 receptor more closely than the
NK1-receptor.
The respiratory rhythm in fish is generated by a diffuse CPG located within
the brainstem (Shelton, 1970).
This CPG controls the activity of trigeminal Vth, facial VIIth,
glossopharyngeal IXth and vagal Xth motor nuclei, all of which drive the
breathing muscles (see Taylor et al.,
1999). The CPG receives modulatory inputs from various sources,
including peripheral mechano- and chemoreceptors, and also from the higher
brain centers, including the mesencephalon and the forebrain
(Shelton, 1959;
Randall and Taylor, 1991;
Taylor et al., 1999). There
have been few studies in fish describing the afferent pathways from peripheral
receptors and their general central projections to the brainstem (see
Burleson et al., 1992).
Immunohistochemical and physiological investigations have demonstrated that in
the channel catfish Ictalurus punctatus, the primary general visceral
nuclei situated at the caudal part of the NTS are crucial for maintaining
basal ventilation and utilizes glutamate as a neurotransmitter for oxygen
chemoreflexes (Sundin et al.,
2003a). Studies conducted in a teleost fish, the shorthorn sculpin
Myoxocephalus scorpius, have also revealed that within the sensory
vagal area of the brainstem, glutamate may be a key excitatory
neurotransmitter released by the afferents of baro- and chemoreceptors
(Sundin et al., 2003b). In the
brainstem of the dogfish Squalus acanthias, catecholamines may also
be involved in the control of the electrical activity of respiratory neurons
(Randall and Taylor, 1991).
However, nothing is known regarding either the origin and the actions of
higher brain centers neurons that project towards the CPG or the respiratory
motoneurons or the neurotransmitters and the receptors involved. The central
pathways mediating the effects of NP and other tachykinins were not
investigated in the present study. It is reasonable, however, to speculate
that ICV injection of tachykinins activated receptor sites located mainly in
the diencephalon, including the hypothalamus, where they can modulate the
activity of various nuclei including the preoptic nuclei. Arginine vasotocin
and isotocin neurons from the preoptic nuclei are known to project their axons
not only to the neurohypophysis but also towards brainstem nuclei, including
the NTS and the dorsal vagal motor nucleus
(Batten et al., 1990;
Saito et al., 2004). In this
context it should be emphasized that immunocytochemical studies have shown
that, in the brain of the rainbow trout, the diencephalon contains the largest
number of SP-immunoreactive fibers and nuclei
(Vecino et al., 1989). In
addition, we can speculate about a possible diffusion of the injected
tachykinins within the cerebrospinal fluid (CSF) towards the brainstem nuclei.
Thus, exogenous tachykinins may produce effects on various nuclei including
those previously described to be crucial for maintaining basal ventilation by
both direct and indirect actions.
Ventilatory and cardiovascular actions of intraarterially administered trout tachykinins
It has previously been shown in the trout that trout SP and NKA increase
both systemic vascular resistance and PDA but decrease
fH and cardiac output
(Kagstrom et al., 1996). Our
present data are consistent with these results and indicate that SP was more
potent than NKA in inducing the increase in PDA and
decrease in fH. In this context, it should also be
mentioned that trout SP was more effective than trout NKA in stimulating
gastric motility in the rainbow trout
(Jensen et al., 1993). In
addition, we have demonstrated for the first time in a fish that
intra-arterial injection of NP in trout causes a hypertensive response
but without change in fH. The lack of bradycardia
following the IA injection of NP is intriguing since the hypertensive
response is relatively robust. Absence of bradycardia suggests that, after IA
injection of NP, the cardio-inhibitory baroreflex response is blunted
or that the reflexogenic decrease in fH is counteracted by
a positive chronotropic effect on the heart. Further studies are needed to
clarify this issue. The effects of the tachykinins on the peripheral
cardiovascular system in trout stand in sharp contrast with the effects of
NP, SP and NKA in mammals, where the three peptides are potent
vasodilators of several vascular beds (see
Conlon, 2004;
Walsh and McWilliams, 2006).
In the anesthetized guinea pig, intravenous injection of NP produced a
fall in blood pressure that was mediated through interaction with NK-1
receptors, together with an increase in total pulmonary resistance and
decrease in dynamic lung compliance that were mediated through NK-2 receptors
(Yuan et al., 1994).
Possible physiological significance
The study provides insight into a possible role of endogenous tachykinins
in the regulation of ventilatory and cardiovascular processes in the trout.
The potent and selective central ventilatory actions of these peptides,
particularly of NP, in increasing fV and decreasing
VAMP thereby resulting in a potent hypoventilatory action,
together with lack of effect on these variables after peripheral
administration, suggest that receptors mediating ventilatory changes exist in
the brain but not in the periphery. Conversely, the cardiovascular actions of
the tachykinins after peripheral administration, particularly the hypertensive
effect of NP, but the absence of cardiovascular actions after central
administration, are consistent with peripheral rather than central
localization of receptor(s) mediating cardiovascular changes.
The relevance of the present data to trout respiratory physiology is
emphasized by the demonstration that numerous tachykinin neurons of a
CSF-contacting type are present within the paraventricular organ of the
hypothalamus in the Atlantic salmon Salmo salar
(Holmqvist and Ekstrom, 1991),
giving strong neuroanatomical support for a possible secretion of the
endogenous products within the CSF compartment. Further studies are required
to determine whether the observed central effects of the exogenously injected
tachykinins, particularly NP, within the third ventricle mimic those of
the endogenous peptides and to reveal under what circumstances tachykininergic
systems of the brain are activated to control the respiratory system. As a
working hypothesis, it is tempting to speculate that the central
tachykininergic system might be recruited under conditions of environmental
hyperoxia, a situation that is known to promote a hypoventilatory response in
trout and other teleost species (Kinkead
and Perry, 1990).
List of abbreviations and symbols
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Acknowledgments |
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References |
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Batten, T. F., Cambre, M. L., Moons, L. and Vandesande, F. (1990). Comparative distribution of neuropeptide-immunoreactive systems in the brain of the green molly, Poecilia latipinna. J. Comp. Neurol. 302,893 -919.[CrossRef][Medline]
Burleson, M. L., Milson, W. K. and Smatresk, N. J. (1992). Afferent inputs associated with cardioventilatory control in fish. In Fish Physiology: The Cardiovascular System. Vol. XIIB (ed. W. S. Hoar, D. J. Randall and A. P. Farrell), pp. 389-426. San Diego: Academic Press.
Conlon, J. M. (2004). The tachykinins peptide family, with particular emphasis on mammalian tachykinins and tachykinin receptor agonists. Handb. Exp. Pharmacol. 164, 25-62.
Fritsche, R. and Nilsson, S. (1993). Cardiovascular and ventilatory control during hypoxia. In Fish Ecophysiology (ed. J. C. Rankin and F. B. Jensen), pp.180 -206. London: Chapman & Hall.
Gray, P. A., Rekling, J. C., Bocchiaro, C. M. and Feldman, J.
L. (1999). Modulation of respiratory frequency by peptidergic
input to rhythmogenic neurons in the preBotzinger complex.
Science 286,1566
-1568.
Gray, P. A., Janczewski, W. A., Mellen, N., McCrimmon, D. R. and Feldman, J. L. (2001). Normal breathing requires preBotzinger complex neurokinin-1 receptor expressing neurons. Nat. Neurosci. 4,927 -930.[CrossRef][Medline]
Holeton, G. F. and Randall, D. J. (1967).
Changes in blood pressure in the rainbow trout during hypoxia. J.
Exp. Biol. 46,297
-305.
Holmqvist, B. I. and Ekstrom, P. (1991). Galanin-like immunoreactivity in the brain of teleosts: distribution and relation to substance P, vasotocin, and isotocin in the Atlantic salmon (Salmo salar). J. Comp. Neurol. 306,361 -381.[CrossRef][Medline]
Holzer, P. (2006). Substance-P and related tachykinins in the gastrointestinal tract. In Handbook of Biologically Active Peptides (ed. A. J. Kastin), pp.1139 -1145. San Diego: Academic Press.
Jensen, J. and Conlon, J. M. (1992). Substance-P-related and neurokinin-A-related peptides from the brain of the cod and trout. Eur. J. Biochem. 206,659 -664.[Medline]
Jensen, J., Olson, K. R. and Conlon, J. M. (1993). Primary structures and effects on gastrointestinal motility of tachykinins from the rainbow trout. Am. J. Physiol. 265,R804 -R810.[Medline]
Kagstrom, J., Holmgren, S., Olson, K. R., Conlon, J. M. and Jensen, J. (1996). Vasoconstrictive effects of native tachykinins in the rainbow trout, Oncorhynchus mykiss.Peptides 17,39 -45.[CrossRef][Medline]
Kinkead, R. and Perry, S. F. (1990). An investigation of the role of circulating catecholamines in the control of ventilation during acute moderate hypoxia in rainbow trout (Oncorhynchus mykiss). J. Comp. Physiol. B 160,441 -448.[CrossRef]
Kumar, G. K. and Prabhakar, N. R. (2003). Tachykinins in the control of breathing by hypoxia: pre- and post-genomic era. Respir. Physiol. Neurobiol. 135,145 -154.[CrossRef][Medline]
Lancien, F., Leprince, J., Mimassi, N., Mabin, D., Vaudry, H. and Le Mével, J. C. (2004). Central effects of native urotensin II on motor activity, ventilatory movements, and heart rate in the trout Oncorhynchus mykiss. Brain Res. 1023,167 -174.[CrossRef][Medline]
Le Mével, J. C., Pamantung, T. F., Mabin, D. and Vaudry, H. (1993). Effects of central and peripheral administration of arginine vasotocin and related neuropeptides on blood pressure and heart rate in the conscious trout. Brain Res. 610, 82-89.[CrossRef][Medline]
Mazzone, S. B. and Geraghty, D. P. (2000). Respiratory actions of tachykinins in the nucleus of the solitary tract: characterization of receptors using selective agonists and antagonists. Br. J. Pharmacol. 129,1121 -1131.[CrossRef]
Meini, S. and Lecci, A. (2006). Tachykinins and their receptors in the lung. In Handbook of Biologically Active Peptides (ed. A. J. Kastin), pp.1301 -1305. San Diego: Academic Press.
Monteau, R., Ptak, K., Broquere, N. and Hilaire, G. (1996). Tachykinins and central respiratory activity: an in vitro study on the newborn rat. Eur. J. Pharmacol. 314, 41-50.[CrossRef][Medline]
Moons, L., Batten, T. F. and Vandesande, F. (1992). Comparative distribution of substance P (SP) and cholecystokinin (CCK) binding sites and immunoreactivity in the brain of the sea bass (Dicentrarchus labrax). Peptides 13, 37-46.[CrossRef][Medline]
Page, N. M. (2006). Brain tachykinins. In Handbook of Biologically Active Peptides (ed. A. J. Kastin), pp. 763-769. San Diego: Academic Press.
Patacchini, R. and Maggi, C. A. (2004). The nomenclature of tachykinins receptors. Handb. Exp. Pharmacol. 164,121 -139.
Picard, P. and Couture, R. (1996). Intracerebroventricular responses to neuropeptide gamma in the conscious rat: characterization of its receptor with selective antagonists. Br. J. Pharmacol. 117,241 -249.
Randall, D. J. and Taylor, E. W. (1991). Evidence of a role for catecholamines in the control of breathing in fish. Rev. Fish Biol. Fish. 1,139 -157.[CrossRef]
Saito, D., Komatsuda, M. and Urano, A. (2004). Functional organization of preoptic vasotocin and isotocin neurons in the brain of rainbow trout: central and neurohypophysial projections of single neurons. Neuroscience 124,973 -984.[CrossRef][Medline]
Satake, H. and Kawada, T. (2006). Overview of the primary structure, distribution, and functions of tachykinins and their receptors. Curr. Drug Targets 7, 963-974.[CrossRef][Medline]
Shelton, G. (1959). The respiratory centre in the tench (Tinca tinca L.). I. The effects of brain transection on respiration. J. Exp. Biol. 36,191 -202.[Abstract]
Shelton, G. (1970). The regulation of breathing. In Fish Physiology: The Nervous System, Circulation, and Respiration. Vol. IV (ed. W. S. Hoar and D. J. Randall), pp. 293-359. New York: Academic Press.
Smith, J. C., Ellenberger, H. H., Ballanyi, K., Richter, D. W.
and Feldman, J. L. (1991). Pre-Botzinger complex: a brainstem
region that may generate respiratory rhythm in mammals.
Science 254,726
-729.
Sundin, L., Turesson, J. and Burleson, M. (2003a). Identification of central mechanisms vital for breathing in the channel catfish, Ictalurus punctatus. Respir. Physiol. Neurobiol. 138,77 -86.[CrossRef][Medline]
Sundin, L., Turesson, J. and Taylor, E. W.
(2003b). Evidence for glutamatergic mechanisms in the vagal
sensory pathway initiating cardiorespiratory reflexes in the shorthorn sculpin
Myoxocephalus scorpius. J. Exp. Biol.
206,867
-876.
Taylor, E. W., Jordan, D. and Coote, J. H.
(1999). Central control of the cardiovascular and respiratory
systems and their interactions in vertebrates. Physiol.
Rev. 79,855
-916.
Vecino, E., Covenas, R., Alonso, J. R., Lara, J. and Aijon, J. (1989). Immunocytochemical study of substance P-like cell bodies and fibres in the brain of the rainbow trout, Salmo gairdneri.J. Anat. 165,191 -200.[Medline]
Walsh, D. A. and McWilliams, F. D. (2006). Tachykinins and the cardiovascular system. Curr. Drug Targets 7,1031 -1042.[CrossRef][Medline]
Yuan, L., Burcher, E. and Nail, B. S. (1994). Use of selective agonists and antagonists to characterize tachykinin receptors mediating airway responsiveness in anaesthetized guinea-pigs. Pulm. Pharmacol. 7,169 -178.[CrossRef][Medline]
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