Tetrandrine potentiates caffeine-induced contraction but inhibits phenylephrine-induced contraction in perfused rat mesenteric artery.
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 micro M) attenuated phenylephrine-induced responses but potentiated the contractile responses to caffeine (5-40 mM) in the presence and absence of Ca(2+). Berbamine (BER), a structural analogue of TET, elicited a relatively smaller inhibitory effect on the responses to PE due to Ca(2+) release or Ca(2+) influx. However, both TET and BER elicited a comparable potentiating effect on caffeine-induced contraction. Cyclopiazonic acid (CPA; 10 micro M), a selective sarcoplasmic reticulum Ca(2+)-ATPase pump inhibitor, mimicked the potentiating effect of TET when added 5 min prior to caffeine in Ca(2+)-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 alpha-adrenoceptors and PE-sensitive Ca(2+)-channels. The augmentation of caffeine-induced responses by TET, particularly in Ca(2+)-free medium, is likely to be due to its partial inhibition of the sarcoplasmic reticulum Ca(2+)-ATPase pump.
Kwan
Chiu-Yin
CY
Department of Medicine, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, Ontario, L8N 3Z5 Canada. kwancy@mcmaster.ca
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D002110:Caffeine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D010477:Perfusion / Q000379:methods; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D000470:Alkaloids; D044182:Benzylisoquinolines; D010656:Phenylephrine; C009438:tetrandrine; D002110:Caffeine