The action of tabernanthine on noradrenaline-stimulated contractions and 45Ca movements in rat isolated vascular smooth muscle.
The iboga alkaloid tabernanthine inhibited depolarization (100 mM K+)-induced contractions in aorta and mesenteric arteries in an concentration-dependent manner with the respective IC50 values being about 21 and 7 microM. Contractions elicited by noradrenaline in the mesenteric artery were potentiated by lower concentrations (0.1 and 1.0 microM) of tabernanthine while they were inhibited by higher concentrations (10-100 microM). Tabernanthine produced only inhibition of noradrenaline-elicited responses in aorta and portal vein, the vein being the most sensitive of the vessels to the inhibitory effects of the compound. The magnitude of the spontaneous contractions of the portal vein, the aortic intracellular calcium fraction releasable by noradrenaline and the turnover of calcium in unstimulated aorta were enhanced by tabernanthine. Depolarization-stimulated 45Ca influx and contractions in the aorta were inhibited to a similar extent by tabernanthine and 100 microM virtually abolished the 45Ca influx stimulated by noradrenaline and depolarization. It is concluded that tabernanthine has a calcium entry blocking action but also has other actions related to the turnover of intracellular calcium releasable by noradrenaline.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002132:Calcium Radioisotopes / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism; D007050:Ibogaine / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D011169:Portal Vein / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000470:Alkaloids; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D004573:Electrolytes; D007050:Ibogaine; C027202:tabernanthine; D009638:Norepinephrine