Calcium-antagonistic activity of sumatriptan in the rat anococcygeus muscle.
The relaxant effect of sumatriptan, a 5-HT(1B/1D) receptor agonist, on the rat anococcygeus muscle was investigated. Sumatriptan induced concentration-dependent relaxations of the phenylephrine-precontracted rat anococcygeus muscle. N(G)-nitro-L-arginine, methylene blue, glibenclamide, tetrodotoxin, indomethacin, GR 113808, GR 55562, methysergide, ketanserin, ICS 205930, clozapine, methiothepin, metergoline, mesulergine, and ritanserin did not inhibit the relaxations induced by sumatriptan. Sumatriptan converted calcium-induced contractions into relaxations in the preparations depolarized by a calcium-free, high-potassium solution. In membrane preparations obtained from the rat anococcygeus muscle, the basal rate of cAMP production by adenylate cyclase was 4.77 +/- 0.02 pmol/mg protein/min (n = 15). The enzyme activity was increased to 104 +/- 51.7 pmol/mg protein/min by forskolin (10(-4) mol/l), but did not change in the presence of sumatriptan. The mRNA expression of 5-HT(1B), 5-HT(1D), and 5-HT(7) receptors was not observed in the rat anococcygeus muscle. The results indicate that sumatriptan causes relaxation of the precontracted rat anococcygeus muscle by a calcium-antagonistic activity.
Emre-Aydingöz
Selda
S
Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
Kocaefe C
Cetin
C
Tuncer
Meral
M
D000262:Adenylyl Cyclases / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D010656:Phenylephrine; D018170:Sumatriptan; D000242:Cyclic AMP; D000262:Adenylyl Cyclases