|
| |
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online June 15, 2006
Journal of Experimental Biology 209, 2525-2534 (2006)
Published by The Company of Biologists 2006
doi: 10.1242/jeb.02274
Pharmacological characterization of the ergot alkaloid receptor in the salivary gland of the ixodid tick Amblyomma hebraeum
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, T6G 2E9, Canada
* Author for correspondence (e-mail: reuben.kaufman{at}ualberta.ca)
Accepted 18 April 2006
 |
Summary |
|---|
 TOP Summary IntroductionMaterials and methodsResultsDiscussionList of abbreviationsReferences |
|---|
-ergocriptine (0.9 µmol
l–1); (ii) three were `incomplete agonists' (approximate
concentration eliciting 20% maximum response is given in parentheses):
ergocorninine (3.5 µmol l–1), ergocristinine (7.5 µmol
l–1) and ergocristine (10 µmol l–1); (C)
three were partial agonists (approximate concentration eliciting the
respective maximum response in parentheses): ergocornine (50% maximum by 1
µmol l–1), methysergide (28% maximum by 10 µmol
l–1) and bromocriptine (22% maximum by 10 µmol
l–1); and (D) one had no activity up to 1 mmol
l–1: ergothioneine. Bromocriptine and methysergide did not
antagonize the action of DA, but were effective competitive antagonists of
ErN, with Kis of 
0.3 µmol l–1 and
11 µmol l–1, respectively. Ergothioneine was not an
antagonist at either the DA- or ErA-sensitive receptor. The putative protein
kinase C activators, 1-oleoyl-2-acetyl-sn-glycerol (OAG) and
1,2-dioctanoyl-sn-glycerol (DiC8), neither stimulated
salivary fluid secretion nor potentiated the action of DA or ErN. The putative
protein kinase C inhibitors, bisindolymaleimide (BIM) and calphostin C did not
inhibit the action of DA or ErN, although low concentrations of calphostin C
(10 nmol l–1) appeared to potentiate the action of DA but not
ErN. The ion transport inhibitors, furosemide and amiloride (both up to 1 mmol
l–1), had no significant effect on DA-stimulated or
ErN-stimulated fluid secretion.
Key words: Amblyomma hebraeum, bromocriptine, dihydroergotamine, ergocornine, ergocorninine, ergocristine, ergocristinine, ergocryptine, ergonovine, ergothioneine, ergot alkaloids, methylergonovine, methysergide, tick salivary gland
|
Introduction |
|---|
|
TOPSummaryIntroductionMaterials and methodsResultsDiscussionList of abbreviationsReferences |
|---|
;
Sauer et al., 2000;
Bowman and Sauer, 2004).
Control of fluid secretion is mediated via at least three receptors.
Dopamine (DA) and other catecholamines stimulate secretion via a DA
receptor. This receptor appears to be in the D-1 family
(Schmidt et al., 1981;
Schmidt et al., 1982).
-Aminobutyric acid (GABA) potentiates the fluid secretion stimulated by
DA via a distinct receptor, but GABA has no intrinsic activity
(Lindsay and Kaufman, 1986).
The fact that muscimol, but not baclofen, mimics the potentiation of GABA,
suggests that this receptor is of the GABAA type. The effect of
GABA is blocked by picrotoxin (100 µmol l–1) and
(–)-bicuculline (100 µmol l–1) in a non-competitive
manner (Lindsay and Kaufman,
1986).
The ergot alkaloid (ErA), ergonovine (ErN), is also a very potent agonist
of salivary fluid secretion (Kaufman and
Wong, 1983). Results with selective antagonists demonstrate that
ErN acts via a receptor distinct from the DA receptor
(Kaufman and Wong, 1983). We
call this third receptor an `ErA-sensitive receptor' because we do not know
the identity of its natural ligand.
Similar to other D-1 receptors, the effect of DA on this tissue is mediated
by cAMP (Schmidt et al., 1981;
Schmidt et al., 1982).
Supramaximal concentrations of ErN also stimulate adenylate cyclase activity
in the tick salivary glands, but only to 50% of the level stimulated by
supramaximal concentrations of DA (W.R.K., unpublished observations),
suggesting that the intracellular pathway mediating the action of ErN may be
somewhat different from that of DA.
ErAs elicit an enormously broad spectrum of pharmacological effects, the
best known being at adrenergic, dopaminergic and tryptaminergic receptors
(Berde and Schild, 1978;
Peroutka, 1996;
Pertz and Eich, 1999),
probably because the structures of these biogenic amines can be exactly
superimposed onto specific parts of the ergoline ring structure
(Berde, 1980). The purpose of
this study was to extend our characterization of the pharmacological
properties of the ErA-sensitive receptor in the tick salivary gland. We
constructed dose–response curves for 11 ErAs available to us.
Non-agonists and partial agonists were tested as putative inhibitors of the
ErA and DA receptors. We also tested some inhibitors and activators of protein
kinase C (PKC) for differential effects on the DA and ErN pathways. Likewise,
we tested two inhibitors of ion transport (amiloride and furosemide) for
differential effects on the two pathways.
|
Materials and methods |
|---|
|
TOPSummaryIntroductionMaterials and methodsResultsDiscussionList of abbreviationsReferences |
|---|
).
For this study we used partially fed ticks in the range of 80–300 mg
(normal engorged mass of A. hebraeum is in the range of
1000–3000 mg).
Drugs and media
Modified Hank's saline (dissection medium)
Composition in g l–1 was: 11.5 NaCl, 1.6
D-glucose, 0.4 KCl, 0.14 CaCl2, 0.098 MgSO4,
0.06 KH2PO4, 0.05 NaHPO4, 0.01 Phenol Red.
The pH was adjusted with NaOH to 7.2; the osmotic pressure was 360
mOsm.
Modified TC 199 (in-vitro bathing medium)
1 package powdered TC199 (11 g; Gibco, Grand Island, NY, USA), 2.1 g NaCl
and 2.09 g 3-[N-morpholino]propanesulfonic acid (Mops; Sigma Chemical
Co., St Louis, MO, USA) were dissolved in distilled-deionized water, the pH
was adjusted with NaOH to 7.2 and the final volume was brought to 1 l.
The following drugs were a gift from Hoffman LaRoche (Basle, Switzerland):
bromocryptine, methylergonovine, ergocristine, ergocristinine, ergocornine,
ergocorninine and methysergide. (+/–)-Sulpiride (Ravizza, Italy or
Delagrange, France) was a gift from Dr G. N. Woodruff, formerly of the
University of Southampton, UK. The following drugs were purchased from Sigma:
DA-HCl, ergonovine-maleate, dihydroergotamine, -ergocryptine,
ergothioneine and 5-hydroxytrypamine (5-HT). Structures of the ErAs used in
this study [plus ergotamine from Kaufman
(Kaufman, 1977)] are shown in
Fig. 1. Deprenyl [monoamine
oxidase (MAO) inhibitor] was purchased from Research Biochemicals Inc.
(Natick, MA, USA). 1-oleoyl-2-acetyl-sn-glycerol (OAG),
1,2-dioctanoyl-sn-glycerol (DiC8), bisindolymaleimide
(BIM) and calphostin C, were purchased from Calbiochem (San Diego, CA,
USA).
|
).
In vitro technique for measuring salivary fluid secretion
The technique was similar to that described earlier
(Kaufman and Phillips, 1973b;
Wong and Kaufman, 1981). Glass
Petri dishes (15 cm diameter) were lined with paraffin wax into which four
fine glass posts were embedded to serve as anchors for the experimental
glands. The Petri dishes were filled with liquid paraffin (light mineral oil;
Fisher Scientific, Fair Lawn, NJ, USA). Briefly, salivary glands were
dissected out under modified Hank's saline with their main ducts completely
intact. The glands were transferred to modified TC 199 and extraneous tissue
clinging to the main duct was teased away. Fine silk thread was ligated to a
fragment of cuticle associated with the terminal portion of the main duct, but
without occluding the orifice. The glands were then transferred to the Petri
dish in a droplet of bathing medium such that the bathing medium adhered to
the glass post and the silk thread draped over the far rim of the Petri dish.
The thread was then gently pulled so that the main duct protruded from the
bathing droplet into the mineral oil. Whenever the bathing medium contained an
effective agonist, a small, spherical droplet of secreted fluid would appear
and grow at the orifice of the main duct. For measuring the amount of secreted
fluid, the droplet was removed from the orifice with a fine glass rod, allowed
to sink, the diameter measured under a stereomicroscope fitted with an ocular
micrometer, and the sphere volume calculated from the diameter of the
droplet.
General experimental protocol
All experiments were done at room temperature (22.5±0.5°C).
Glands were exposed to a control treatment (usually a given concentration of
agonist), and the rate of secretion was recorded every 3–5 min until an
equilibrated rate for that treatment was observed (usually 10–20 min).
During this time, the prevailing medium was changed for a fresh droplet every
3–5 min. Then the glands were exposed to successively higher
concentrations of drug, each time an equilibrated rate of secretion being
recorded following similar changes of prevailing medium. Concentration of drug
was increased by 10-fold increments until the response was maximal. When the
drug under consideration was not DA, the glands were then washed in drug-free
TC 199 for at least 20 min, and then exposed to 10 µmol
l–1 DA for three to five 3-min readings. Unless otherwise
stated, the response of the glands to 10 µmol l–1 DA was
designated as 100%, and the maximal responses of the other treatments were
compared to this value.
Putative antagonists were tested by one of two protocols. The first was a conventional dose–response protocol, in the presence of the drug being tested for antagonism. In the second protocol, the glands were exposed to an agonist drug (usually a sub-maximal concentration) until there was no further increase in secretory rate. Then putative antagonist was tested (several concentrations) until an equilibrated rate of secretion was observed at each concentration. To test for reversal of antagonism, the glands were re-exposed to agonist alone for up to 30 min.
Inhibitory constants (Ki) were calculated from the
following equation:
 |
).
Statistics
Unless otherwise stated, data are reported as mean ± s.e.m.
(N), and statistically analysed using one-way ANOVA or Student's
t-tests.
|
Results |
|---|
|
TOPSummaryIntroductionMaterials and methodsResultsDiscussionList of abbreviationsReferences |
|---|
-ergocryptine (0.9
µmol l–1). (2) Incomplete agonists were those
that neither elicited the maximum response nor appeared to reach some
plateaued response at the highest concentration that could be tested (usually
because of limited availability). The approximate concentrations eliciting 20%
maximum response were: ergocorninine (3.5 µmol l–1),
ergocristinine (7.5 µmol l–1), and ergocristine (10
µmol l–1; Fig.
3). (3) Partial agonists
(Fig. 4) were those for which
the response plateaued at substantially less than 100% of the maximum
response. These were (with the approximate lowest concentration eliciting the
respective maximum response in parentheses): ergocornine (50% maximum by 1
µmol l–1), methysergide (28% maximum by 10 µmol
l–1) and bromocryptine (22% maximum by 10 µmol
l–1). (4) Non-agonists. Ergothioneine was the only
ErA with no intrinsic activity at the highest concentration tested (seven
glands tested up to 1 mmol l–1).
|
|
|
As mentioned in the Introduction, ErAs interact frequently with 5-HT and
catacholamine receptors, behaving either as agonists or antagonists, but the
natural ligand for the ErA-sensitive receptor in tick salivary glands has not
yet been identified. The effect of 5-HT on tick salivary glands has been
tested in a number of studies, and at best it is a very weak agonist
(Kaufman and Phillips, 1973b;
Kaufman, 1977;
Needham and Sauer, 1975). We
tested its action again as part of this study, with the hope of determining
whether it acted via the DA receptor (blocked by butaclamol) or the
ErA-sensitive receptor [blocked by sulpiride
(Kaufman and Wong, 1983)]. Of
16 glands tested that responded to 10 µmol l–1 DA, only
five were also stimulated by 5-HT (up to 10 mmol l–1); 5-HT
was an incomplete agonist, with 20% maximum response occurring at 220
µmol l–1 (Fig.
3).
We asked whether this inconsistent and weak response to 5-HT might be due
to high levels of monoamine oxidase (MAO) in the tissue. So we repeated some
dose–response experiments with 5-HT in the presence of 220 µmol
l–1 deprenyl, an MAO inhibitor known to be effective on tick
salivary glands (Kaufman and Sloley,
1996). Even though MAO should have been almost completely
inhibited under these conditions, 5-HT still failed to stimulate salivary
fluid secretion in eight glands, all of which responded to 10 µmol
l–1 DA (data not shown). Thus we abandoned our attempt to
determine at which receptor 5-HT elicits its weak, inconsistent effect.
Putative antagonists
Ergothioneine (non-agonist), bromocryptine and methysergide (partial
agonists) were tested for their ability to inhibit ErN- and DA-stimulated
secretion. Ergothioneine (1 mmol l–1) caused no rightward
shift of the ErN dose–response curve
(Fig. 5) nor of the DA
dose–response curve (five trials; data not shown). Bromocryptine (3
trials) and methysergide (3 trials) did not significantly antagonize the
action of DA (Fig. 6A), but
both were effective, surmountable antagonists of ErN
(Fig. 6B), with
Kis of 0.3 µmol l–1
(bromocryptine) and 11 µmol l–1 (methysergide).
|
|
). We
confirmed these findings here, determining an inhibitory constant of 0.73
µmol l–1 for sulpiride on ErN
(Fig. 5), and an inability for
sulpiride to attenuate the action of DA (data not shown).
Intracellular pathways
The intracellular pathways mediating DA-induced secretion involve cAMP,
Ca2+, cytosolic phospholipase A2 (cPLA2), and
arachidonic acid (reviewed by Sauer et
al., 2000; Bowman and Sauer,
2004). Nothing is known about the intracellular pathways mediating
ErA-induced secretion. However, there is evidence that protein kinase C (PKC)
is a component of the intracellular signalling pathway in tick salivary glands
(see Discussion). So, in this study we tested the actions of a number of drugs
known to stimulate or inhibit PKC in other systems to learn whether the action
of DA and ErN were affected differently.
BIM (Toullec et al., 1991)
and calphostin C (Kobayashi et al.,
1989; Bruns et al.,
1991) were tested for possible inhibitory effects, and OAG
(Benz et al., 1992;
Florin-Christensen et al.,
1993) and DiC8
(Lapetina et al., 1985) were
tested for possible excitatory effects on DA- and ErA-stimulated fluid
secretion. Salivary glands were exposed to a sub-maximal concentration of DA
(0.1 µmol l–1) or ErN (0.1 µmol l–1)
for six 5-min readings to determine the equilibrated response at that
concentration; the mean value (± s.e.m.) of the last two or three
readings was recorded as the control response. Then the test drug (PKC
activator or inhibitor) was added in the presence of DA or ErN and secretion
was monitored for up to a further six 5-min readings. The glands were then
re-exposed to either DA or ErN alone to record recovery. The results for the
putative PKC activators, OAG and DiC8, are presented in
Table 1, and those for the
putative PKC inhibitors, BIM and calphostin C, are presented in
Table 2 and
Fig. 7.
|
|
|
Neither OAG nor DiC8 potentiated the action of sub-maximal
concentrations of DA or ErN (Table
1). In all cases the secretory rates declined in the presence of
OAG or DiC8 and on return to the control treatment, but at least
part of this reduction may have been the natural decline that occurs with time
when glands are continually stimulated for extensive periods
(Kaufman, 1976).
BIM did not inhibit the secretory response of salivary glands in the presence of sub-maximal (0.1 µmol l–1) or supra-maximal (10 µmol l–1) concentrations of ErN or DA (Table 2) The response to calphostin C depended on the concentration range. Low concentrations of calphostin C (10 nmol l–1) appeared to potentiate the action of DA (leftward shift of the dose-response curve; Fig. 7A) but not that of ErN (Fig. 7B). At 0.1 µmol l–1 calphostin C, there was no statistically significant inhibitory (or potentiating) effect using a sub-maximal (0.1 µmol l–1) concentration of ErN or DA (Table 2).
Ion transport inhibitors
Furosemide [an inhibitor of various Cl– cotransporter
systems (Cabantchik and Greger,
1992)] and amiloride [an inhibitor of many Na+
transport systems (Kleyman and Cragoe, Jr,
1988)] were both tested for effects on DA- and ErN-stimulated
secretion. Salivary glands were exposed to 10 µmol l–1 DA
or 10 µmol l–1 ErN until maximum secretion was achieved.
They were then exposed to DA or ErN along with 1 µmol l–1
to 1 mmol l–1 furosemide or amiloride for three successive
readings of 5 min for each concentration. Neither furosemide nor amiloride had
any significant effect on DA- or ErN-stimulated secretory rates; note,
however, that the sample sizes were small
(Table 3).
|
|
Discussion |
|---|
|
TOPSummaryIntroductionMaterials and methodsResultsDiscussionList of abbreviationsReferences |
|---|
; Goldstein et al.,
1980; Pertz and Eich,
1999). Most studies on insects and other invertebrates conform to
vertebrate models in this respect (e.g.
Sakharov et al., 1989;
Wedemeyer et al., 1992;
Blenau et al., 1998;
Degen et al., 2000). However,
5-HT is only a very weak agonist at best for stimulating fluid secretion in
tick salivary glands (Kaufman and
Phillips, 1973b; Needham and
Sauer, 1975; Kaufman,
1977; this study). Evidence for a DA receptor (a D-1 type),
however, is considerable (for reviews, see
Sauer et al., 2000;
Bowman and Sauer, 2004). As
mentioned in the Introduction, ErAs do not exert their effects via
this receptor. In brief, the ErA effects on the tick salivary gland cannot be
interpreted in the same light as ErA effects in most other systems. There seem
to be only very few other examples in the literature in which an ErA might act
via an unidentified receptor (den
Boer et al., 1991).
In this study, the ErAs tested fell into one of four classes, grouped
arbitrarily according to their efficacy at the ErA-sensitive receptor:
complete agonists, incomplete agonists, partial agonists and non-agonists. The
structures of the ErAs tested are shown in
Fig 1. Those that exhibited at
least some agonist activity (all except ergothioneine) are based on an
ergoline ring structure. Although ergotamine was not tested here, it has also
been reported as a full agonist, with a potency similar to that of ergonovine
(Kaufman, 1977). There is
little beyond that broad generalization, however, to explain the other
differences in activity presented here. For example, only three of the five
complete agonists are ergopeptines (ergotamine, dihydroergotamine and
-ergocriptine), the other two (ErN and methylergonovine) are not.
Moreover, with the exception of methysergide, all of the incomplete and
partial agonists are also ergopeptines (ergocornine, ergocorninine,
ergocristine, ergocristinine and bromocriptine).
It is commonly observed that the action of ErAs is difficult to reverse
even with extensive washout procedures
(Bond et al., 1989;
Schöning et al., 2001),
and this was found to be the case with the tick salivary gland. One potential
explanation for the long-lasting effect is continual diffusion from a pool of
drug absorbed into the tissue during the incubation period
(Bulow et al., 1986;
Tfelt-Hansen and Johnson,
1993). Berridge and Prince
(Berridge and Prince, 1973),
reporting on the agonist action of LSD at the 5-HT receptor of the blowfly
salivary gland, discounted the latter possibility for that system. They
proposed instead that part of the ErA molecule (presumably the diethyl amide)
binds tightly to an allosteric site of the 5-HT receptor, allowing the active
portion (presumably the ergoline) to repeatedly attach to and disengage from
the active site. Similar to the blowfly salivary gland, the tick salivary
gland is free of layers of muscle or connective tissue that could serve to
store a pool of drug (although extrinsic fat body tissue is omnipresent). In
rat tail artery preparations, insurmountable blockade of the 5-HT response by
methysergide has been attributed to allosteric modulation of 5-HT2A
receptors rather than to pseudoirreversible inhibition
(Pertz and Eich, 1992). In
this case, however (unlike that for the blowfly and tick salivary glands),
onset of action is also very prolonged
(Schöning et al., 2001).
A general model has been proposed whereby one can differentiate between slow
ligand–receptor dissociation from slow diffusion
(Martin et al., 1995).
The results presented here further support earlier observations that 5-HT
is unlikely to be the endogenous ligand at the ErA-sensitive receptor. The
small and inconsistent effect of 5-HT might be due to an indirect action. For
example, tick salivary glands contain a relatively high endogenous content of
DA (Kaufman and Sloley, 1996),
possibly in the numerous granular cells. Perhaps the inconsistent agonist
action of 5-HT is due to an occasional stimulation of DA release from this
endogenous source.
There is now a growing understanding about the intracellular signalling
cascade following stimulation of the tick (Amblyomma americanum)
salivary gland DA receptor (reviewed by
Sauer et al., 2000;
Bowman and Sauer, 2004). The
salivary gland contains several isoforms of a cAMP-dependent protein kinase
(cAPKC1-3) that are activated in isolated salivary glands exposed
to DA. As a result, at least a dozen salivary gland proteins are
phosphorylated. The glands also contain phosphoprotein phosphatase activity,
further supporting a role for PKC in salivary fluid secretion. Under the
conditions tested here, there is little evidence to suggest that PKC is an
intermediate in the pathway linked to the ErA-sensitive receptor or the DA
receptor. The two PKC activators, OAG and DiC8, did not stimulate
salivary fluid secretion on their own (data not shown), and they did not
potentiate the stimulatory effect of sub-maximal concentrations of DA or ErN
(both at 0.1 µmol l–1;
Table 1). The PKC inhibitors,
BIM and calphostin C, likewise did not inhibit the stimulatory action of 0.1
µmol l–1 DA or ErN
(Table 2); if anything, the
trend was to potentiate the action of DA and ErN, though the differences
between control and treated samples in
Table 2 were not statistically
significant in a consistent manner. The potentiating trend was also observed
at lower concentrations of calphostin C, where 10 nmol l–1
appeared to shift the dose–response curve of DA to the left, but not
that of ErN (Fig. 7); the
number of replicates in this experiment, however, was small. This matter
clearly merits further investigation.
We have some confidence that the experimental protocol used for the PKC
experiments was appropriate, both with regard to the concentration ranges
tested and the duration of incubation. Just a few examples include: PKC
mediation in 5-HT stimulated ciliary beat frequency in embryos of the pond
snail, Heliosoma trivolvis
(Christopher et al., 1999),
inhibition of PKC by BIM in chick proximal tubule
(Dudas et al., 2002),
activation of PKC in rabbit portal vein myocytes
(Albert and Large, 2001),
stimulation of PKC of human kidney proximal tubules
(Pietig et al., 2001), and
inhibition of PKC by calphostin C on human endothelial cells
(Orzechowski et al.,
2001).
Our knowledge of the pharmacological properties of the tick ErA-sensitive
receptor is obviously rudimentary compared to that of many mammalian systems,
at least in part because relatively few congeners have been tested. Recently
it has been shown that 8R-lisuride is a partial agonist at human histamine
H1 receptors (Bakker et al.,
2004), which expands the repertoire of ErA targets yet further.
However, histamine (up to 1 mmol l–1) did not stimulate fluid
secretion in tick salivary glands
(Kaufman, 1977).
Unfortunately, we still have no idea as to what the natural ligand is at the
tick salivary gland ErA-sensitive receptor, or whether it is a component of a
neuronal or hormonal pathway. We also do not know the physiological conditions
under which this pathway to fluid secretion is stimulated [the DA pathway
seems to be involved in haemolymph volume regulation
(Kaufman et al., 1980)]. This
remains a major gap in our understanding of tick salivary gland function.
|
List of abbreviations |
|---|
|
TOPSummaryIntroductionMaterials and methodsResultsDiscussionList of abbreviationsReferences |
|---|
-aminobutyric acid
|
Acknowledgments |
|---|
|
References |
|---|
|
TOPSummaryIntroductionMaterials and methodsResultsDiscussionList of abbreviationsReferences |
|---|
Albert, A. P. and Large, W. A. (2001).
Comparison of spontaneous and noradrenaline-evoked non-selective cation
channels in rabbit portal vein myocytes. J. Physiol.
530,457
-468.
Bakker, R. A., Weiner, D. M., ter Laak, T., Beuming, T.,
Zuiderveld, O. P., Edelbroek, M., Hacksell, U., Timmerman, H., Brann,
M. R. and Leurs, R. (2004). 8R-Lisuride is a potent
stereospecific histamine H1-receptor partial agonist.
Mol. Pharmacol. 65,538
-549.
Benz, I., Herzig, J. W. and Kohlhardt, M. (1992). Opposite effects of angiotensin II and the protein kinase C activator OAG on cardiac Na+ channels. J. Membr. Biol. 130,183 -190.[Medline]
Berde, B. (1980). Ergot compounds: a synopsis. In Ergot Compounds and Brain Function (ed. M. Goldstein, A. Lieberman, D. M. Calne and M. O. Thorner), pp.3 -23. New York: Raven Press.
Berde, B. and Schild, H. O. (1978). Ergot Alkaloids and Related Compounds. Berlin, Heidelberg, New York: Springer-Verlag.
Berridge, M. J. and Prince, W. T. (1973). Mode of action of hallucinogenic molecules. Nat. New Biol. 243,283 -284.[Medline]
Blenau, W., Erber, J. and Baumann, A. (1998). Characterization of a dopamine D1 receptor from Apis mellifera: cloning, functional expression, pharmacology, and mRNA localization in the brain. J. Neurochem. 70,15 -23.[Medline]
Bond, R. A., Ornstein, A. G. and Clarke, D. E.
(1989). Unsurmountable antagonism to 5-hydroxytryptamine in rat
kidney results from pseudoirreversible inhibition rather than multiple
receptors or allosteric receptor modulation. J. Pharmacol. Exp.
Ther. 249,401
-410.
Bowman, A. S. and Sauer, J. R. (2004). Tick salivary glands: function, physiology and future. Parasitology 129,S67 -S81.
Bruns, R. F., Miller, D., Merriman, R. L., Howbert, J. J., Heath, W. F., Kobayashi, E., Takahashi, I., Tamaoki, T. and Nakano, H. (1991). Inhibition of protein kinase C by calphostin C is light-dependent. Biochem. Biophys. Res. Commun. 176,288 -293.[CrossRef][Medline]
Bulow, P. M., Ibraheem, J. J., Paalzow, G. and Tfelt-Hansen, P. (1986). Comparison of pharmocodynamic effects and plasma levels of oral and rectal ergotamine. Cephalalgia 6, 107-111.[CrossRef][Medline]
Cabantchik, Z. I. and Greger, R. (1992). Chemical probes for anion transporters of mammalian cell membranes. Am. J. Physiol. 262,C803 -C827.[Medline]
Christopher, K. J., Young, K. G., Chang, J. P. and Goldberg, J.
I. (1999). Involvement of protein kinase C in 5-HT stimulated
ciliary activity in Heliosoma trivolvis embryos. J.
Physiol. 515,511
-522.
Degen, J., Gewecke, M. and Roeder, T. (2000). The pharmacology of a dopamine receptor in the locust nervous tissue. Eur. J. Pharmacol. 396,59 -65.[Medline]
den Boer, M. O., Heiligers, J. P. and Saxena, P. R. (1991). Carotid vascular effects of ergotamine and dihydroergotamine in the pig: no exclusive mediation via 5-HT1-like receptors. Br. J. Pharmacol. 104,183 -189.
Dudas, P. L., Villalobos, A. R., Gocek-Sutterlin, G., Laverty,
G. and Renfro, J. L. (2002). Regulation of
transepithelial phosphate transport by PTH in chicken proximal tubule
epithelium. Am. J. Physiol. Regul. Integr. Comp.
Physiol. 282,R139
-R146.
Florin-Christensen, J., Florin-Christensen, M., Delfino, J. M. and Rasmussen, H. (1993). New patterns of diacylglycerol metabolism in intact cells. Biochem. J. 389,783 -788.
Goldstein, A., Aranow, L. and Kalman, S. M. (1974). Principles of Drug Action: The Basis of Pharmacology (2nd edn). New York: John Wiley and Sons.
Goldstein, M., Lieberman, A., Calne, D. B. and Thorner, M. O. (1980). Ergot Compounds and Brain Function: Neuroendocrine and Neuropsychiatric Aspects. New York: Raven Press.
Kaufman, W. R. (1976). The influence of various
factors on fluid secretion by in vitro salivary glands of ixodid ticks.
J. Exp. Biol. 64,727
-742.
Kaufman, W. R. (1977). The influence of adrenergic agonists and their antagonists on fluid secretion by isolated salivary glands of ixodid ticks. Eur. J. Pharmacol. 45, 61-68.[CrossRef][Medline]
Kaufman, W. R. (1989). Tick-host interaction: a synthesis of current concepts. Parasitol. Today 5, 47-56.[Medline]
Kaufman, W. R. and Phillips, J. E. (1973a). Ion
and water balance in the ixodid tick, Dermacentor andersoni. I.
Routes of ion and water excretion. J. Exp. Biol.
58,523
-536.
Kaufman, W. R. and Phillips, J. E. (1973b). Ion
and water balance in the ixodid tick, Dermacentor andersoni. II.
Mechanisms and control of salivary secretion. J. Exp.
Biol. 58,537
-547.
Kaufman, W. R. and Sloley, B. D. (1996). Catabolism of dopamine and 5-hydroxytryptamine by monoamine oxidase in the ixodid tick, Amblyomma hebraeum. Insect Biochem. Mol. Biol. 26,101 -109.[Medline]
Kaufman, W. R. and Wong, D. L. (1983). Evidence for multiple receptors mediating fluid secretion in salivary glands of ticks. Eur. J. Pharmacol. 87,43 -52.[Medline]
Kaufman, W. R., Aeschlimann, A. and Diehl, P. A. (1980). Regulation of body volume by salivation in a tick challenged with fluid loads. Am. J. Physiol. 238,R102 -R112.[Medline]
Kleyman, T. R. and Cragoe, E. J., Jr (1988). Amiloride and its analogs as tools in the study of ion transport. J. Membr. Biol. 105,1 -21.[CrossRef][Medline]
Kobayashi, E., Nakano, H., Morimoto, M. and Tamaoki, T. (1989). Calphostin C (UNC-1028C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C. Biochem. Biophys. Res. Commun. 159,548 -553.[CrossRef][Medline]
Lapetina, E. G., Reep, B., Ganong, B. R. and Bell, R. M.
(1985). Exogenous sn-1,2-diacylglycerols containing
saturated fatty acids function as bioregulators of protein kinase C in human
platelets. J. Biol. Chem.
260,1358
-1361.
Lindsay, P. J. and Kaufman, W. R. (1986).
Potentiation of salivary fluid secretion in ixodid ticks: a new receptor
system for -aminobutyric acid. Can. J. Physiol.
Pharmacol. 64,1119
-1126.[Medline]
Martin, G. R., Martin, R. S. and Wood, J. (1995). Long-acting 5-HT1D receptoragonist effects of dihydroergotamine: studies using a model to differentiate slow drug-receptor dissociation from diffusion. In Experimental Headache Models (ed. J. Olesen and M. A. Moskowitz), pp.163 -167. Philadelphia: Lippincott-Raven.
Needham, G. and Sauer, J. R. (1975). Control of fluid secretion by isolated salivary glands of the lone star tick. J. Insect Physiol. 21,1893 -1898.[Medline]
Orzechowski, H. D., Gunther, A., Menzil, S., Zimmermann, A.,
Funke-Kaiser, H., Real, R., Subkowski, T., Zollmann, F. S. and Paul, M.
(2001). Transcriptional mechanism of protein kinase C-induced
isoform-specific expression of the gene for endothelin-converting enzyme-1in
human endothelial cells. Mol. Pharmacol.
60,1332
-1342.
Peroutka, S. J. (1996). Drugs effective in the therapy of migrain. In Goodman and Gilman's Pharmacological Basis of Therapeutics (ed. P. B. Molinoff and R. W. Rudden), pp.487 -503. New York: McGraw-Hill.
Pertz, H. and Eich, E. (1992). O-Acylated lysergol and dihydrolysergol-I derivatives as competitive antagonists of 5-HT at 5-HT2 receptors of rat tail artery: allosteric modulation instead of pseudoirreversible inhibition. Naunyn Schmeidebergs Arch. Pharmacol. 345,394 -401.[Medline]
Pertz, H. and Eich, E. (1999). Ergot alkaloids and their derivatives as ligands for serotonergic, dopaminergic and adrenergic receptors. In Ergot: The genus Claviceps (ed. V. Kren and L. Cvak), pp. 411-440. Amsterdam: Harwood Academic Publishers.
Pietig, G., Mehrens, T., Hirsch, J. R., Cetinkaya, I., Piechota,
H. and Schlatter, E. (2001). Properties and regulation
of organic cation transport in freshly isolated human proximal tubules.
J. Biol. Chem. 276,33741
-33746.
Sakharov, D. A., Hiripi, L. and Salánki, J. (1989). Pharmacologically induced stereotyped locomotory movements in the pelecypod mollusk, Anodonta cygnea. Comp. Biochem. Physiol. 92C,343 -347.
Sauer, J. R., Essenberg, R. C. and Bowman, A. S. (2000). Salivary glands in ixodid ticks: control and mechanism of secretion. J. Insect Physiol. 46,1069 -1078.[Medline]
Schmidt, S. P., Essenberg, R. C. and Sauer, J. R. (1981). Evidence for a D1 dopamine receptor in the salivary glands of Amblyomma americanum (L.) J. Cyclic Nucleotide Res. 7,375 -384.[Medline]
Schmidt, S. P., Essenberg, R. C. and Sauer, J. R. (1982). Dopamine sensitive adenylate cyclase in the salivary glands of the lone star tick. Comp. Biochem. Physiol. 72, 9-14.
Schöning, C., Flieger, M. and Pertz, H. H.
(2001). Complex interaction of ergovaline with 5-HT2A,
5-HT1B/1D, and alpha1 receptors in isolated arteries of
rat and guinea pig. J. Anim. Sci.
79,2202
-2209.
Tfelt-Hansen, P. and Johnson, E. S. (1993). Ergotamine. In The Headaches (ed. J. Olesen, P. Tfelt-Hansen and K. M. Welch), pp. 313-322. New York: Raven Press.
Toullec, D., Pianetti, P., Coste, H., Bellevergue, P.,
Grand-Perret, T., Ajakane, M., Baudet, V., Boissin, P., Boursier, E.,
Loriolle, F. et al. (1991). The bisindolylmaleimide GF
109203X is a potent and selective inhibitor of protein kinase C. J.
Biol. Chem. 266,15771
-15781.
Wedemeyer, S., Roeder, T. and Gewecke, M. (1992). Pharmacological characterization of a 5HT receptor in locust nervous tissue. Eur. J. Pharmacol. 223,173 -178.[Medline]
Wong, D. L. and Kaufman, W. R. (1981). Potentiation by spiperone and other butyrophenones of fluid secretion by isolated salivary glands of ixodid ticks. Eur. J. Pharmacol. 73,163 -173.[Medline]
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
