Investigation of 5-HT3 receptor-mediated contraction in guinea-pig distal colon.
We investigated the participation of cholinergic and tachykininergic mechanisms in 5-hydroxytryptamine (5-HT)-induced contraction via 5-HT3 receptors in longitudinal and circular muscle of guinea-pig isolated distal colon. 5-HT produced concentration-dependent contractile responses in longitudinal and circular muscle. The 5-HT3 receptor antagonists ramosetron (YM060) ((R)-5-[(1-methyl-3-indolyl) carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride), YM114 (KAE-393) ((R)-5-[(2,3-dihydro-1-indolyl)carbonyl]-4,5,6,7-tetrahydro-1 H-benzimidazole hydrochloride), ondansetron and granisetron produced a concentration-dependent shift to the right of the 5-HT concentration-response curves in both muscle. However, methysergide and GR113808 had no effect on 5-HT-induced contraction. In the longitudinal muscle, atropine concentration-dependently inhibited 5-HT-induced contraction, and tetrodotoxin abolished it. (+/-)-CP96,345 attenuated the contractile response to 5-HT, but (+/-)-SR48,968 had no effect on it. In the presence of atropine, (+/-)-CP96,345 completely blocked 5-HT-induced contraction. In the circular muscle, atropine had no effect on the contractile response to 5-HT, whereas tetrodotoxin completely suppressed it. The contractile response elicited by 5-HT in the circular muscle was not inhibited by either (+/-)-CP96,345, (+/-)-SR48,968, devazepide, L-365,260 or indomethacin. It is suggested that 5-HT acts via 5-HT3 receptors to release acetylcholine and substance P, which in turn are responsible for contraction of the longitudinal muscle. In the circular muscle, as in the longitudinal muscle, 5-HT-induced contraction is mediated by the 5-HT3 receptor. Unlike the case in longitudinal muscle, however, this contraction involves neither cholinergic nor tachykininergic transmission. It is also suggested that neither cholecystokinin (CCK) nor prostaglandins participate in 5-HT3 receptor-mediated contraction in circular muscle.
Yamano
M
M
Neuroscienc Research Laboratories, Yamanouchi Pharmaceutical Co. Ltd., Tsukuba, Japan.
Miyata
K
K
D000818:Animals; D002766:Cholecystokinin / Q000502:physiology; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D064729:Neurokinin-1 Receptor Antagonists; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D018039:Receptors, Tachykinin / Q000819:agonists / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D015320:Tachykinins / Q000502:physiology
D064729:Neurokinin-1 Receptor Antagonists; D011453:Prostaglandins; D018041:Receptors, Neurokinin-2; D011985:Receptors, Serotonin; D018039:Receptors, Tachykinin; D012702:Serotonin Antagonists; D015320:Tachykinins; D012701:Serotonin; D002766:Cholecystokinin