Pharmacology of the Malpighian tubules of Rhodnius and Carausius: the structure-activity relationship of tryptamine analogues and the role of cyclic AMP.

Recently it has been shown that 5-hydroxytryptamine (5-HT) even at concentrations of the order of io" M/1 will stimulate fluid secretion by the Malpighian tubules of two insect species, Rhodnius prolixus Stal and Carausius morosus (Maddrell, Pilcher & Gardiner, 1969). In order to find out more about this interaction the activity of a range of substances chemically related to 5-HT has been studied. This has yielded information about the nature and the behaviour of the sites where 5-HT interacts with the cells of the Malpighian tubules. Apart from its intrinsic interest such a study may throw light on the nature of the naturally occurring diuretic hormones. There are several pieces of information to show that 5-HT is not the diuretic hormone extractable from the nervous systems of Rhodnius or of Carausius (see p. 799). Nonetheless, as will be shown in this paper, inhibitors of 5-HT action also antagonize the action of these diuretic hormones. Since this suggests that the hormones and 5-HT act on the same sites, information about these sites should also tell us something about the possible structure of at least the activity-inducing parts of the hormones. The second part of this paper examines the possible involvement of the cyclic nucleotide, 3',5'-adenosine monophosphate (cyclic AMP) in the chain of events which link the primary stimulation by 5-HT, or by the hormones, to the actual mechanisms producing secretion. Cyclic AMP is thought to behave as an intracellular mediator for the action of many hormones (see for example Robison, Butcher & Sutherland, 1968). Most of the experiments described are for Malpighian tubules of Rhodnius. Many experiments have, however, also been carried out using tubules from Carausius, and these provide a most valuable comparison with the experiments on Rhodnius tubules.