[Effect of vinpocetine (TCV-3B), a vasodilator agent, on cyclic nucleotide metabolism].
Effect of a novel compound, 14-ethoxycarbonyl-(3 alpha, 16 alpha-ethyl)-14,15-eburnamenine (vinpocetine, TCV-3B), on the cyclic nucleotide metabolism and in vitro response of a vascular strip was investigated. The concentration of vinpocetine producing relaxation of the canine basilar arterial strip induced by 30 microM arachidonate peroxide was 3 microM. Cyclic GMP content in the vascular strip increased dose-dependently by addition of vinpocetine, and 2.5-fold elevation of cyclic GMP content in the vascular strip was observed by 10 microM vinpocetine. Administration of vinpocetine concentrations ranging from 1 to 100 microM did not produce a significant increase in cyclic AMP of the vascular strip. Vinpocetine did not stimulate guanylate cyclase, but selectively inhibited Ca2+-calmodulin dependent phosphodiesterase (Ca2+-PDE). Increase in cyclic GMP by vinpocetine is due to inhibition of Ca2+-PDE because Ca2+-PDE is known to hydrolyze cyclic GMP preferentially. Our results suggest that vinpocetine, a selective Ca2+-PDE inhibitor, produces relaxation of the vascular strip by the increase in cyclic GMP.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*; D014748:Vinca Alkaloids / Q000494:pharmacology*
D014665:Vasodilator Agents; D014748:Vinca Alkaloids; C013983:vinpocetine; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D006152:Cyclic GMP