Vascular effects of tetramethylpyrazuie: direct interaction with smooth muscle α-adrenoceptors

Abstract

The interaction of tetramethylpyrazine, a vasoactive ingredient of a Chinese traditional medicinal plant, with the vascular muscle α 1-adrenoceptors was investigated by a direct radioligand binding technique using [ 3H]prazosin and vascular smooth muscle microsomes isolated from dog aorta and mesenteric artery. Tetramethylpyrazine inhibited the binding of [ 3H]prazosin to vascular muscle membranes in a concentration-dependent manner at a suboptimal concentration of prazosin. Scatchard analysis of the effect of tetramethylpyrazine on the saturation profile of [ 3H]prazosin binding to vascular muscle microsomes of either arterial muscle indicated a substantial increase of K d values (the affinity for prazosin) without a change in B max (maximal binding sites for prazosin). Thus, the present results provide supporting evidence that the inhibitory effect of tetramethylpyrazine on the vasoconstriction of dog mesenteric artery induced by phenylephrince in the earlier studies may be. at least, in part due to a direct action at the recognition sites of α-adrenoceptors. Amiloride and amiloride-related compounds, which shares a common pyrazine ring structure with tetramethylpyrazine and other related derivatives, also inhibits the binding of [ 3H]prazosin to aortic muscle microsomal membranes. Functional studies of dog saphenous vein also indicated that both tetramethylpyrazine and its ethyl derivatives inhibited the responses induced by phenylephrine and B-HT 920 in the presence and absence of extracellular Ca 2+. Together with our earlier findings that amiloride also inhibits [ 3H]praizosin and [ 3H]rauwolscine binding to vascular muscle α 1- and α 2-adrenoceptors, the present radioligand binding study in canine arteries and functional study in saphenous veins suggest that the above compounds containing the pyrazine nucleus indeed interacted at the α-adrenoceptor sites.