Inhibition of intracellular calcium elevation and blunting of vasopressor response due to serotonin by ginkgolide B.
The vascular effects of each individual composition in the extract of Ginkgo biloba have not been clarified. In this work, we have investigated whether ginkgolide B (GKB), a terpene lactone component from Ginkgo biloba, modulates intracellular calcium ([Ca (2+)] i) of vascular smooth muscle cells (smc) and how it influences the vasopressor response in vitro caused by serotonin (5-HT). GKB (3.2 - 9.6 microM) selectively decreased serotonin-induced [Ca (2+)] i elevations in cultured smc from bovine aorta in dose-dependent manner, while it had no effects on both resting [Ca (2+)] i and potassium-elicited [Ca (2+)] i elevations. On the other hand, GKB in a concentration of 3.2 - 9.6 microM moderately decreased the maximal pressor efficacy of serotonin by 14 - 45 % in rat mesenteric vascular beds, and the EC50 remained unchanged. The comparison study also showed GKB had no effects on noradrenaline-elicited pressor reactions. These results implicate that GKB may selectively inhibit serotonin-mediated [Ca (2+)] i mobilization in vascular smc and non-competitively alleviate the vasopressor effect of serotonin in vitro.
Wang
Yu
Y
Department of Pharmacology, School of Medicine, Nanjing University, Nanjing, PR China. YwangH8@sohu.com
Yu
Ying-Qun
YQ
Xu
Jian-Guo
JG
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D020441:Ginkgo biloba; D046934:Ginkgolides; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D015394:Molecular Structure; D009638:Norepinephrine / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004224:Diterpenes; D016166:Free Radical Scavengers; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D014662:Vasoconstrictor Agents; D012701:Serotonin; D011189:Potassium Chloride; D014700:Verapamil; C045856:ginkgolide B; D002118:Calcium; D009638:Norepinephrine