TETRANDRINE, A CALCIUM-ANTAGONIST OF CHINESE HERBAL ORIGIN, INTERACTSWITH VASCULAR MUSCLE ALPHA(1)-ADRENOCEPTOR

The effects of tetrandrine (TET) on the contractile responses of rat a ortic rings and perfused rat mesenteric arteries to phenylephrine (PE) were investigated. TET inhibited the maximal contraction to PE in a c oncentration-dependent manner. TET significantly inhibited the transie nt contraction in Ca2+-free medium presumably due to release of intrac ellular Ca2+ after activation of alpha(1)-adrenoceptors. However, it c aused a stronger inhibition of the sustained contraction in Ca2+-conta ining medium presumably the result of Ca2+ influx. TET has no inhibito ry effect on caffeine-induced transient contraction. Radioligand recep tor binding study using isolated dog aortic muscle membranes indicated that TET inhibited the binding of H-3-prazosin in a competitive manne r, hence showing that TET interacted directly with the alpha(1)-adreno ceptors. Thus, TET affected PE-induced aortic contractions by multiple mechanisms, inhibiting interaction of PE with alpha(1)-adrenoceptors and interfering with PE-induced responses involving both Ca2+ entry an d release.