Pharmacological characterization of 5-Hydroxytryptamine-receptor subtypes in circular muscle from the rat stomach.
5-Hydroxytryptamine (5-HT) modulates gastric motility and gastric emptying via a variety of 5-HT receptor subtypes. However, regional and functional differences among 5-HT receptor subtypes in the rat stomach are not fully investigated. Thus, we aimed to characterize 5-HT receptor subtypes involved in the 5-HT-induced contractions in the isolated antral, corporal and fundic circular muscles of the rat stomach by measuring the contractile force. 5-HT induced concentration-dependent contractions in the antrum, corpus and fundus. 5-HT-induced antral contractions were partly blocked by atropine and enhanced by tetrodotoxin (TTX). Neither atropine nor TTX affected the corporal or the fundic contractions to 5-HT. In the antrum, 5-HT-induced contractions were inhibited by methysergide, tended to be inhibited by ketanserin, enhanced by SB-203186, but were not affected by WAY-100635, GR127935, RS-127445, ondansetron, or SB-269970. In the corpus, 5-HT-induced contractions were inhibited by ketanserin or methysergide. In the fundus, 5-HT-induced contractions were blocked by methysergide or RS-127445, but were enhanced by cinanserin or SB-203186. It is thus concluded that contractile responses to 5-HT in the antrum are mediated by 5-HT receptors on both smooth muscle and neurons whilst in the corpus and fundus responses are mainly mediated by 5-HT receptors on smooth muscle. Moreover, the antrum presents the contractile 5-HT2A and 5-HT2B receptors and the relaxant 5-HT4 receptors. The corpus presents the contractile 5-HT2A receptors, and the fundus presents the contractile 5-HT2B receptors and the relaxant 5-HT2A and 5-HT4 receptors.
Komada
Tohru
T
Discovery Biology Research, Global Research & Development, Nagoya Laboratories, Pfizer Japan Inc., 5-2 Taketoyo, Aichi 470-2393, Japan. Tohru.Komada@pfizer.com
Yano
Shingo
S
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005748:Gastric Fundus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D017294:Ondansetron / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D020033:Protein Isoforms / Q000502:physiology; D011706:Pyloric Antrum / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
C088817:(1-piperidinyl)ethyl 1H-indole-3-carboxylate; D007211:Indoles; D010069:Oxadiazoles; D010636:Phenols; D010879:Piperazines; D010880:Piperidines; D020033:Protein Isoforms; D011725:Pyridines; D011743:Pyrimidines; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C121466:2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine; C090701:GR 127935; D012701:Serotonin; D013779:Tetrodotoxin; D017294:Ondansetron; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D001285:Atropine; D007650:Ketanserin; D008784:Methysergide