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 controlling acetylcholine release and contraction induced by stimulation of the neurokinin NK3 receptor has been studied in the longitudinal muscle-myenteric plexus preparation from guinea-pig ileum. 2. In preparations preloaded with [3H]-choline, the selective NK3 agonist, senktide, produced a concentration-dependent increase in tritium overflow, an index of [3H]-acetylcholine release. Low concentrations of neurokinin B, also markedly increased tritium efflux. 3. The senktide-induced acetylcholine release was markedly increased by the same concentration of methysergide and mesulergine. The 5-HT2A/2C agonist DOI (1 microM) inhibited the tritium overflow while 8-OH-DPAT, sumatriptan and ketanserin (1 microM each) were without effect on the senktide-induced tritium efflux. 4. The contractile response to senktide in the guinea-pig ileum was attenuated by atropine, 0.1 microM. Methysergide, a 5-HT1/2 receptor antagonist, and mesulergine, a 5-HT2A/2B/2C receptor antagonist, (1 microM each), enhanced the contractile effect of the NK3 receptor agonist. 5. It is concluded that the acetylcholine release induced by a NK3 receptor agonist is inhibited by stimulation of a 5-HT receptor, possibly of the 5-HT2C or 5-HT2C subtype.
Ramírez
M J
MJ
Department of Pharmacology, School of Pharmacy, University of Navarra, Pamplona, Spain.
Del Río
J
J
Cenarruzabeitia
E
E
Lasheras
B
B
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism; D015287:Neurokinin B / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018042:Receptors, Neurokinin-3 / Q000819:agonists; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology
D010446:Peptide Fragments; D018042:Receptors, Neurokinin-3; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C054724:senktide; C062618:substance P, Sar(9)-Met(O2)(11)-; D013373:Substance P; D015287:Neurokinin B; D000109:Acetylcholine