title: Pharmacologic characterization of contractile serotonergic receptors in human isolated mesenteric artery.
abstract: The 5-hydroxytryptamine (5-HT) receptors mediating contraction in human isolated mesenteric arteries were characterized. Endothelium-denuded human isolated mesenteric arteries were used. 5-HT induced concentration-dependent contractions in mesenteric arteries (Emax, 127.37 +/- 7.61% of 80 mM KCl maximal contraction; pD2, 6.73 +/- 0.09 [-logEC50]). Sumatriptan, a selective 5-HT1B/1D receptor agonist, induced concentration-dependent contractions in some of the arteries (Emax, 61.82 +/- 10.04%; pD2, 6.56 +/- 0.21, n = 9) but not in the others (Emax < 5%, n = 13), suggesting that functional 5-HT1B/1D receptors exist in some but not in all mesenteric arteries. GR127935 (a selective 5-HT1B/1D receptor antagonist, 3 nM) inhibited sumatriptan-induced contractions in arteries in which sumatriptan responses were strong in an insurmountable manner. GR127935 (10 nM) also inhibited 5-HT responses and shifted the concentration-response curve of 5-HT to the right significantly (p < 0.05; pD2s were 6.54 +/- 0.18 and 5.93 +/- 0.11 in the presence of vehicle and GR127935, respectively). Ketanserin (0.01-1 microM) competitively antagonized 5-HT responses in human mesenteric arteries: pA2 value was 8.40 +/- 0.25 (slope of Schild regression, 1.43 +/- 0.18; r2, 0.98). Tropisetron (5-HT3 receptor antagonist) and prazosin (alpha1-adrenoceptor antagonist) did not affect the contractions induced by 5-HT. These results suggest that 5-HT2A and 5-HT1B/1D receptors, but not 5-HT3 and alpha1-adrenoceptors, are involved in the 5-HT-induced contractions in human isolated mesenteric arteries. Sumatriptan-induced and 5-HT1B/1D receptor-mediated responses vary greatly among patients.
authors.affiliation: Department of Pharmacology, Gülhane Military Medical Academy, Faculty of Medicine, Etlik, Ankara, Turkey.
authors.forename: Husamettin
authors.initials: H
authors.lastname: Gul
authors.forename: Oguzhan
authors.initials: O
authors.lastname: Yildiz
authors.forename: Abdurrahman
authors.initials: A
authors.lastname: Simsek
authors.forename: Mujdat
authors.initials: M
authors.lastname: Balkan
authors.forename: Nail
authors.initials: N
authors.lastname: Ersoz
authors.forename: Sadettin
authors.initials: S
authors.lastname: Cetiner
authors.forename: Askin
authors.initials: A
authors.lastname: Isimer
authors.forename: Dervis
authors.initials: D
authors.lastname: Sen
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D018170:Sumatriptan