title: Evidence for 5-HT7 receptors mediating relaxation of human colonic circular smooth muscle.
abstract: 5-HT4 receptors mediate relaxation of human colon circular muscle. However, after 5-HT4 receptor blockade (SB 204070 10 nM), 5-HT still induced a relaxation (pEC50 6.3). 5-HT4 receptors were sufficiently blocked, as the curves to 5-HT obtained in the presence of 10 and 100 nM SB 204070 were indistinguishable. This 5-HT-induced relaxation was tetrodotoxin-insensitive, indicative of a smooth muscle relaxant 5-HT receptor. This, and the rank order of potency (5-CT=5-MeOT=5-HT) suggested involvement of 5-HT1 or 5-HT7 receptors. Mesulergine, a 5-HT7 receptor antagonist at nanomolar concentrations, and a 5-HT1 receptor antagonist at micromolar concentrations, competitively antagonized the 5-HT-induced relaxation (pKB 8.3) and antagonized the relaxation to 5-CT. Methysergide antagonized the 5-HT-induced relaxation (pA2 7.6). It is concluded that the profile of the smooth muscle inhibitory 5-HT receptor resembles that of the 5-HT7 receptor. These data provide the first evidence for functional human 5-HT7 receptors.
authors.affiliation: Department of Gastrointestinal Pharmacology, Janssen Research Foundation, Beerse, Belgium.
authors.forename: N H
authors.initials: NH
authors.lastname: Prins
authors.forename: M R
authors.initials: MR
authors.lastname: Briejer
authors.forename: P J
authors.initials: PJ
authors.lastname: Van Bergen
authors.forename: L M
authors.initials: LM
authors.lastname: Akkermans
authors.forename: J A
authors.initials: JA
authors.lastname: Schuurkes
mesh_terms: D003106:Colon / Q000187:drug effects / Q000502:physiology*; D004146:Dioxanes / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D004146:Dioxanes; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C104425:serotonin 7 receptor; C084858:SB 204070A