Smooth muscle relaxing and hypotensive activities of synthetic calciseptine and the homologous snake venom peptide FS2.
The biological activities of synthetic calciseptine and FS2, a homologous peptide from snake venom, were determined using in vitro and in vivo preparations. Calciseptine and FS2 produced dose-dependent relaxation in pre-constricted rat aorta, pulmonary artery and trachea. The onset and duration pattern of these relaxing effects were similar to those caused by nifedipine, an L-type Ca2+ channel blocker. Calciseptine relaxed the contraction of rat aorta provoked by an L-type channel agonist, Bay K 8644. This relaxation was not affected by NG-nitro-L-arginine, indomethacin or propranolol. Calciseptine and FS2 inhibited the contraction caused by acetylcholine in guinea pig ileal longitudinal muscle. In case of in vivo study using anesthetized rats, calciseptine, FS2 and nifedipine showed depressor effects. The hypotensive effects of the two peptides were more potent and sustained than that of nifedipine. These findings show that both synthetic calciseptine and FS2 have similar biological activities like nifedipine, an L-type Ca2+ channel blocker. In addition, these two peptides with large molecular weights may be unique and useful tools for studying the Ca2+ channel.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000494:pharmacology*; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012910:Snake Venoms / Q000494:pharmacology*; D013997:Time Factors
D002121:Calcium Channel Blockers; D004546:Elapid Venoms; D012910:Snake Venoms; C067971:calciseptine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester