Tetrandrine potentiates caffeine-induced contraction but inhibits phenylephrine-induced contraction in perfused rat mesenteric artery

Abstract. Effects of tetrandrine (TET), a bisbenzylisoquinoline alkaloid, on the contractile responses of perfused rat mesenteric arteries to phenylephrine (PE) and caffeine were investigated. TET concentration-dependently (1–30 µM) attenuated phenylephrine-induced responses but potentiated the contractile responses to caffeine (5–40 mM) in the presence and absence of Ca2+. Berbamine (BER), a structural analogue of TET, elicited a relatively smaller inhibitory effect on the responses to PE due to Ca2+ release or Ca2+ influx. However, both TET and BER elicited a comparable potentiating effect on caffeine-induced contraction. Cyclopiazonic acid (CPA; 10 µM), a selective sarcoplasmic reticulum Ca2+-ATPase pump inhibitor, mimicked the potentiating effect of TET when added 5 min prior to caffeine in Ca2+-free medium. However, CPA did not augment and might even inhibit the caffeine-induced response when it was preincubated with the tissue for 25 min prior to the addition of caffeine. We propose that TET elicits differential effects on PE- and caffeine-induced responses in perfused rat mesenteric arterial bed. The inhibitory effect of TET on PE-induced responses is probably due to its direct interactions with α-adrenoceptors and PE-sensitive Ca2+-channels. The augmentation of caffeine-induced responses by TET, particularly in Ca2+-free medium, is likely to be due to its partial inhibition of the sarcoplasmic reticulum Ca2+-ATPase pump.