The vasorelaxant effect of evocarpine in isolated aortic strips: mode of action.
The effect of evocarpine (EVO), a quinolone alkaloid isolated from Evodiae fructus, on Ca2+-blocking activity has been examined. In the isolated rat thoracic aorta evocarpine significantly inhibited the contraction induced by 60 mM K+ with an IC50 of 9.8 microM, and that induced by external Ca2+ in the depolarized muscle in concentrations of 10-100 microM. The relaxant effect of evocarpine and verapamil was antagonized by Bay K8644. The increase of 45Ca2+-influx induced by 60 mM K+ was significantly inhibited by 100 microM evocarpine. In the isolated rabbit thoracic aorta 100 microM evocarpine had no effect on the norepinephrine-induced contraction in normal medium or on the phasic contraction in Ca2+-free medium or on the transient relaxation induced by activation of the Na+ pump. The content of cyclic AMP or cyclic GMP was unchanged. These results suggest that evocarpine inhibits Ca2+ influx through voltage-dependent calcium channels.
Yamahara
J
J
Kyoto Pharmaceutical University, Japan.
Kobayashi
G
G
Matsuda
H
H
Fujimura
H
H
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects; D002132:Calcium Radioisotopes; D002339:Carotid Arteries / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism
D000470:Alkaloids; D002132:Calcium Radioisotopes; D015363:Quinolones; C059242:evocarpine; D012964:Sodium; D000242:Cyclic AMP; D006152:Cyclic GMP; D011188:Potassium; D009638:Norepinephrine