ON THE NATURE OF THE 5-HT RECEPTOR SUBTYPE INHIBITING ACETYLCHOLINE-RELEASE IN THE GUINEA-PIG ILEUM

1 The nature of the 5-hydroxytryptamine (5-HT) receptor subtype contro lling acetylcholine release and contraction induced by stimulation of the neurokinin NK3 receptor has been studied in the longitudinal muscl e-myenteric plexus preparation from guinea-pig ileum. 2 In preparation s preloaded with [H-3]-choline, the selective NK3 agonist, senktide, p roduced a concentration-dependent increase in tritium overflow, an ind ex of [H-3]-acetylcholine release. Low concentrations of neurokinin B, also markedly increased tritium efflux. 3 The senktide-induced acetyl choline release was markedly increased by the same concentration of me thysergide and mesulergine. The 5-HT2A/(2C) agonist DOI (1 mu M) inhib ited the tritium overflow while 8-OH-DPAT, sumatriptan and ketanserin (1 mu M each) were without effect on the senktide-induced tritium effl ux.4 The contractile response to senktide in the guinea-pig ileum was attenuated by atropine, 0.1 mu M. Methysergide, a 5-HT1/2, receptor an tagonist, and mesulergine, a 5-HT2A/2B/(2C) receptor antagonist, (1 mu M each), enhanced the contractile effect of the NK3 receptor agonist. 5 It is concluded that the acetylcholine release induced by a NK3 rec eptor agonist is inhibited by stimulation of a 5-HT receptor, possibly of the 5-HT2C or 5-HT2B subtype.