5-HT receptor types in the rat ileum longitudinal muscle: focus on 5-HT2 receptors mediating contraction.
The 5-hydroxytryptamine (5-HT) receptor(s) that mediate(s) contraction of the rat ileum longitudinal muscle was studied. 5-HT and alpha-methyl-5-HT equipotently induced contractions, whereas 5-methoxytryptamine and 2-methyl-5-HT (partial agonist) were less potent; this rank order of potency suggests involvement of a 5-HT2 receptor. Neither tetrodotoxin nor atropine affected the contraction to 5-HT, suggesting a smooth muscle localization of these 5-HT2 receptors. The presence of either a selective 5-HT2B (SB 204741), 5-HT3 (granisetron) or 5-HT4 (SB 204070) antagonist, slightly affected the contractions to 5-HT. Thus, they were also included in the organ bath solution in all subsequent experiments in order to pharmacologically isolate the main contractile component. Using (if possible) 5-HT2A receptor-selective concentrations, ketanserin, ritanserin, metergoline, spiperone, mianserin, methiothepin, mesulergine, methysergide and cisapride all inhibited the contractions to 5-HT, causing a depression of the curve to 5-HT (i.e. surmountable antagonism was not observed with any of the above agents). Comparison of the affinities of these compounds for the various 5-HT2 receptor subtypes revealed that the receptor involved in the contractions to 5-HT most closely resembles the 5-HT2A receptor. However, cinanserin at a concentration expected to inhibit 5-HT2A receptor-mediated effects, failed to affect the contractions to 5-HT. It is thus concluded that on the longitudinal smooth muscle of the rat ileum, at least a part of the contraction to 5-HT is mediated by 5-HT receptors resembling the 5-HT2A receptor subtype.
Briejer
M R
MR
Department of Gastrointestinal Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Mathis
C
C
Schuurkes
J A
JA
D008735:5-Methoxytryptamine / Q000494:pharmacology; D000818:Animals; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D007082:Ileum / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C042390:alpha-methylserotonin; D012701:Serotonin; D008735:5-Methoxytryptamine; C045918:2-methyl-5-HT; D007650:Ketanserin