Tetrandrine, a calcium antagonist of Chinese herbal origin, interacts with vascular muscle alpha 1-adrenoceptor.

The effects of tetrandrine (TET) on the contractile responses of rat aortic rings and perfused rat mesenteric arteries to phenylephrine (PE) were investigated. TET inhibited the maximal contraction to PE in a concentration-dependent manner. TET significantly inhibited the transient contraction in Ca(2+)-free medium presumably due to release of intracellular Ca2+ after activation of alpha 1-adrenoceptors. However, it caused a stronger inhibition of the sustained contraction in Ca(2+)-containing medium presumably the result of Ca2+ influx. TET has no inhibitory effect on caffeine-induced transient contraction. Radioligand receptor binding study using isolated dog aortic muscle membranes indicated that TET inhibited the binding of 3H-prazosin in a competitive manner, hence showing that TET interacted directly with the alpha 1-adrenoceptors. 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 and release.