Calcium antagonistic properties of the sesquiterpene T-cadinol: a comparison with nimodipine in the isolated rat aorta.
(+)-T-Cadinol is a sesquiterpene with smooth muscle relaxing properties. In the isolated rat aorta, T-cadinol relaxed contractions induced by 60 mM K+ in a concentration-dependent fashion. The dihydropyridine calcium antagonist nimodipine was approximately 4,000 times more potent than T-cadinol. While both drugs nearly abolished the K(+)-induced contractions, they only partially relaxed contractions induced by phenylephrine. The relaxation induced by T-cadinol and nimodipine in K(+)-contracted aortic rings, was completely reversed by the calcium channel activator Bay K8644. In aortic preparations partially depolarized by 20 mM K+, Bay K8644 induced a concentration-dependent contraction. Nimodipine shifted the Bay K8644 concentration-response curve to the right in a parallel manner, consistent with a competitive mode of inhibition. T-cadinol at concentrations less than 10(-3.5) M also produced a right-ward shift of the Bay K8644 concentration-response curve with a maintained maximum response. However, the highest T-cadinol concentration used 10(-3.5 M) significantly reduced the maximum response. In conclusion, although T-cadinol and nimodipine display marked structural differences, their pharmacological profiles of action have several features in common, suggesting that T-cadinol is a calcium antagonist, possibly interacting with the dihydropyridine binding sites on the calcium channels.
Claeson
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P
Department of Pharmacognosy, Uppsala University, Sweden.
Zygmunt
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Högestätt
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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*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D012717:Sesquiterpenes; D009553:Nimodipine; C072576:T-cadinol; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester