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Pharmacology of the Malpighian Tubules of Rhodnius and Carausius: The Structure-Activity Relationship of Tryptamine Analogues and the Role of Cyclic Amp
1 Agricultural Research Council Unit of Invertebrate Chemistry and Physiology, Department of Zoology Downing Street, Cambridge, CB2 3E£
2 Agricultural Research Council Unit of Invertebrate Chemistry and Physiology, Department of Zoology Downing Street, Cambridge, CB2 3E£; Department of Clinical Research, University College Hospital Medical School, University Street, London, W .C. 1
1. 5-Hydroxytryptamine (5-HT) and a few of its derivatives will cause an acceleration of secretion by the isolated Malpighian tubules of Rhodnius prolixus and Carausius morosus. Substitution in the terminal amino group of 5-HT causes little loss of effect, but changes in the indole ring and the hydroxy group in general abolish activity.
2. Most derivatives of 5-HT which do not stimulate secretion, and many other related amines, act as inhibitors of secretion in Rhodnius. This inhibition is probably of the competitive type.
3. Substances which stimulate secretion in Rhodnius are easily washed off the Malpighian tubules, although they will stimulate secretion at very low concentrations By contrast, competitive inhibitors wash away relatively slowly and inhibit only at much higher concentrations. It is suggested therefore that stimulation involves only momentary interactions between stimulant and receptor sites, but that competitive inhibitors spend considerably longer attached to the sites.
4. Cyclic 3',5'-adenosine monophosphate (cyclic AMP) will stimulate secretion by tubules of both Rhodnius and Carausius. Tubules of both species are very sensitive to cyclic AMP, measurable effects being produced at concentrations of 4 x 10-5 M/l in Rhodnius and 10-4 M/l in Carausius.
5. Aminophylline (theophylline ethylene diamine) at a concentration of 10-4 M/l stimulates secretion by Carausius tubules. This compound and other inhibitors of phosphodiesterase have no stimulatory action on Rhodnius tubules, but any such effect may be masked by the adverse reaction of the tubules to the high concentrations necessary.
6. Inhibitors of 5-HT action such as tryptamine and tyramine also inhibit secretion by Rhodnius Malpighian tubules induced by cyclic AMP. This may be due to a dependence of the action of cyclic AMP on the state of the diuretic hormone receptor site.
7. The evidence is consistent with the idea that 5-HT, other stimulant molecules related to 5-HT and the diuretic hormones interact with Malpighian tubule cells of Rhodnius and Carausius at specific sites, probably on the cell membrane facing the haemolymph. As a result of this, secretion is induced, possibly through the action of intracellular cyclic AMP produced as a response.
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