Pharmacologic Characterization of Contractile Serotonergic Receptors in Human Isolated Mesenteric Artery *Husamettin Gul, *Oguzhan Yildiz, †Abdurrahman Simsek, †Mujdat Balkan, †Nail Ersoz, †Sadettin Cetiner, *Askin Isimer, and †Dervis Sen Departments of *Pharmacology and †Surgery, Gu ¨lhane Military Medical Academy, Faculty of Medicine, Etlik, Ankara, Turkey Summary: 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 con- centration-dependent contractions in mesenteric arteries (E max , 127.37 ± 7.61% of 80 mM KCl maximal contraction; pD 2 , 6.73 ± 0.09 [-logEC 50 ]). Sumatriptan, a selective 5-HT 1B/1D receptor agonist, induced concentration- dependent contractions in some of the arteries (E max , 61.82 ± 10.04%; pD 2 , 6.56 ± 0.21, n  9) but not in the others (E max < 5%, n  13), suggesting that functional 5-HT 1B/1D receptors exist in some but not in all mesenteric arteries. GR127935 (a selective 5-HT 1B/1D receptor antagonist, 3 nM) inhibited suma- triptan-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; pD 2 s were 6.54 ± 0.18 and 5.93 ± 0.11 in the presence of vehicle and GR127935, respectively). Ketanserin (0.01–1 M) competi- tively antagonized 5-HT responses in human mesenteric arteries: pA 2 value was 8.40 ± 0.25 (slope of Schild regression, 1.43 ± 0.18; r 2 , 0.98). Tropisetron (5-HT 3 receptor antagonist) and prazosin ( 1 -adrenoceptor antagonist) did not affect the contractions induced by 5-HT. These results suggest that 5-HT 2A and 5-HT 1B/1D receptors, but not 5-HT 3 and  1 -adrenoceptors, are involved in the 5-HT–induced contractions in human isolated mesenteric arteries. Suma- triptan-induced and 5-HT 1B/1D receptor-mediated responses vary greatly among patients. Key Words: 5-hydroxytryptamine—Characterization— Sumatriptan—5-HT 1B/1D receptors—5-HT 2A receptors—Human mesenteric artery. 5-Hydroxytryptamine (5-HT, serotonin) has been shown to be a potent vasoconstrictor of the vasculature (1,2). The various effects of 5-HT on the central nervous system and peripheral organs are mediated through acti- vation of multiple types of receptors (1). Although there are seven 5-HT receptor families identified so far, 5-HT 2A and 5-HT 1B/1D receptor subtypes are almost ex- clusively responsible for 5-HT–induced vasoconstriction Received January 29, 2002; accepted July 16, 2002. Supported by GATA Research and Development Center (1998/28). Address correspondence and reprint requests to Oguzhan Yildiz at the Department of Pharmacology, Gulhane Military Medical Academy, School of Medicine, 06018, Etlik, Ankara, Turkey. E-mail: oyildiz@ gata.edu.tr Journal of Cardiovascular Pharmacology™ 41:307–315 © 2003 Lippincott Williams & Wilkins, Inc., Philadelphia 307