Modulation of noradrenaline-induced membrane currents by papaverine in rabbit vascular smooth muscle cells.
1. The modulation of noradrenaline-induced membrane currents by papaverine was studied with the nystatin whole-cell technique in freshly isolated rabbit ear artery and portal vein cells. 2. At a holding potential of -50 mV (in potassium-free conditions), papaverine inhibited the Ca(2+)-activated inward chloride current ICl(Ca) evoked by ionophoretic application of noradrenaline in rabbit portal vein cells in a concentration-dependent (10(-5)-10(-4) M) manner. 3. With potassium-containing solutions (at 0 mV) 10(-4) M-papaverine reversibly abolished the Ca(2+)-activated outward potassium current IK(Ca) induced by noradrenaline in both protal vein and ear artery cells. Occasionally, 10(-4) M-papaverine itself activated IK(Ca) before it abolished the response to noradrenaline. 4. Higher concentrations of papaverine (up to 10(-3) M) always evoked both ICl(Ca) and IK(Ca) at -50 and 0 mV respectively, before it abolished these responses to noradrenaline in both ear artery and portal vein cells. In the presence of 10(-3) M-papaverine higher doses of noradrenaline evoked the non-selective cation current in some portal vein cells. 5. In the presence of 10(-2) M-caffeine, which elicited both IK(Ca) and ICl(Ca), papaverine (10(-3) M) failed to activate either current and 10(-3) M-papaverine reduced the caffeine-induced IK(Ca) by 94%. In contrast, IK(Ca) induced by the calcium ionophore ionomycin was unaffected by papaverine. In Ca(2+)-free, 1 mM-EGTA external solutions, 10(-3) M-papaverine still induced IK(Ca) and blocked the response to noradrenaline. 6. The alpha 1-adrenoceptor antagonist prazosin (5 x 10(-8) M) completely blocked the noradrenaline-induced IK(Ca) but currents evoked by papaverine (10(-3) M) were unaffected by prazosin. 7. It was concluded that papaverine modulated noradrenaline-induced membrane currents in vascular smooth muscle cells by releasing and depleting caffeine-sensitive intracellular Ca2+ stores.
Wang
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Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, London.
Large
W A
WA
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002712:Chlorides / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007473:Ion Channels / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010208:Papaverine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits
D002712:Chlorides; D007473:Ion Channels; D015221:Potassium Channels; D002110:Caffeine; D015759:Ionomycin; D010208:Papaverine; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin