Adult guinea pig hippocampal membranes contain two 5-hy-those of 5-HT but are additive with those of RU 24969, a typical droxytryptamine(5-HT) receptors positively coupled with an 5-HT1 agonist. The effects of benzamides, as well as those of 5-adenylate cyclase. One is a typical 5-HT1A receptor and the HT, on 5-HT4 receptors are not blocked by 5-HT1, 5-HT2, or 5-second is a nonclassical 5-HT receptor that we previously pro-HT3 antagonists except ICS 205 903, which does so with a low posed to call 5-HT4. Here, we show that 4-amino-5-chloro-2- affinity (1 LM). The potency of benzamides(cisapride> BRL methoxy-benzamide derivatives are agonists of 5-HT4 receptors 24924> zacopride> BRL 20627> metoclopramide) is similar in guinea pig hippocampal membranes. Their effects on the to their effect on 5-HT4 receptors positively coupled with an adenylate cyclase of these membranes are not additive with adenylate cyclase of fetal mouse colliculi neurons.

We have recently described nonclassical S-HT receptors that is very similar to that of one of the two 5-HT receptors involved we designated S-HT4 (1-3). These receptors mediate the stim- in the indirect stimulation of smooth muscle contraction in ulation of adenylate cyclase activity both in embryo colliculi guinea pig ileum (3). In order to be sure that the 5-HT4 neurons in primary culture and in adult guinea pig hippocampal receptors of adult animals are similar to the S-HT4 receptors membranes(1). of fetal colliculi neurons, we have studied in the present work They have a very specific pharmacology. They are neither of the effect of 4-amino-S-chloro-2-methoxy-benzamide derivathe S-HT1 type, inasmuch as very potent S-HT1 agonists(8-tives on the S-HT4 receptors of adult guinea pig hippocampal hydroxy-(2-di-n-propylamino) tetralin, RU 24924, ipsapirone) membranes. or antagonists(methiothepin, metergoline, spiperone, pindolol, mesulergine) are inactive, nor of the S-HT2 type, inasmuch as Materials and Methods ketanserine has no effect. They are not of the S-HT3 type, inasmuch as 1) 2-methyl-5-HT was ineffective, whereas analogues of 5-HT substituted in position 5 of the indole ring were full or partial agonists(4), and 2) most of the 5-HT3 antagonists were inactive(BRL 43694, GR 38032F, MDL 72222, cocaine) except ICS 205 930, which has a low potency(about 1 jsM). In addition to these properties, we found that, in fetal colliculi