6533b85efe1ef96bd12bf4dd

RESEARCH PRODUCT

α-Adrenoceptor Interaction of Tetrandrine and Isotetrandrine in the Rat: Functional and Binding Assays

Maria CatretMartin ElorriagaElsa AnselmiM P D'ocónMaria Dolores IvorraRemedios Tur

subject

StereochemistryPharmaceutical Sciencechemistry.chemical_elementAorta ThoracicIn Vitro TechniquesBiologyPharmacologyCalciumTritiumBenzylisoquinolinesBinding CompetitiveMuscle Smooth VascularCalcium in biologyNorepinephrinechemistry.chemical_compoundAlkaloidsPrazosinmedicineExtracellularAnimalsDrug InteractionsRats WistarCerebral CortexPharmacologyBinding SitesMolecular StructureAlkaloidBiological activityPrazosinReceptors Adrenergic alphaCalcium Channel BlockersRatsTetrandrinechemistryCalciumFemaleIntracellularMuscle ContractionProtein Bindingmedicine.drug

description

Abstract The action of 1S,1′S-tetrandrine, a bisbenzyltetrahydroisoquinoline alkaloid, on α1-adrenoceptors has been compared with that of its isomer 1R,1′S-isotetrandrine. The work includes binding assays to analyse the affinity of these products for the [3H]prazosin binding site of rat cerebral cortical membranes and functional studies on rat isolated aorta to examine the effects of both alkaloids on intracellular calcium processes related or not to α-adrenoceptor activation. A radioligand receptor-binding study showed that both compounds interacted with the α1-adrenoceptors displacing [3H]prazosin from the specific binding site. The Ki values (inhibition constants) were 0.69±0.12 and 1.6±0.4 μM for tetrandrine and isotetrandrine, respectively. The functional studies showed that both alkaloids concentration-dependently inhibited noradrenaline-induced contraction in Ca2+-free solution (IC50 values, i.e. the concentrations needed to induce 50% inhibition, were 252.8 and 174.9 μM for tetrandrine and isotetrandrine, respectively), the spontaneous contractile response elicited by extracellular calcium after depletion of noradrenaline-sensitive intracellular stores (increase in resting tone; IC50 values 11.6 and 19.6 μM for tetrandrine and isotetrandrine, respectively) and the refilling of intracellular Ca2+ stores sensitive to noradrenaline (IC50 values 7.4 and 14.9 μM for tetrandrine and isotetrandrine, respectively). The results show that tetrandrine and isotetrandrine interact with α1-adrenoceptors by displacing the [3H]prazosin binding site and that both compounds inhibit mainly the Ca2+-dependent process and have less action on α1-adrenoceptors. Tetrandrine is more potent than isotetrandrine.

https://doi.org/10.1111/j.2042-7158.1998.tb03344.x