Inhibition of voltage-dependent Ca(2+)-current by alpha-adrenoceptor agonists in smooth muscle cells.
The cellular mechanisms underlying the inhibitory effects of phenylephrine on dihydropyridine-sensitive, voltage-dependent Ca2+ currents recorded from single smooth muscle cells dissociated from the rat anococcygeus muscle were examined. Phenylephrine (0.1-30 microM) produced a concentration-dependent inhibition of the Ca2+ current; the maximum response occurred at a concentration of 10 microM, which inhibited the peak inward current evoked at 0 mV by 57.7 +/- 4% (n = 8). The response to phenylephrine was reduced but not abolished in cells containing 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid (BAPTA; 10 mM), and it persisted in cells dialysed internally with heparin (5 mg.ml-1). This was despite the fact that both EGTA (5 mM) and heparin were able to block the phenylephrine-induced, Ca(2+)-dependent chloride current recorded in the same cells. The inhibition of the Ca2+ current produced by phenylephrine was abolished in cells containing guanosine 5'-[beta-thio]diphosphate (GDP-beta-S) but persisted in cells pre-treated with pertussis toxin. Our results suggest that the inhibition of L-type Ca2+ current seen following alpha-adrenoceptor activation occurs by a mechanism independent from the inositol trisphosphate-mediated release of Ca2+ from intracellular stores.
England
S
S
Vascular Biology Research Centre, King's College London, UK.
McFadzean
I
I
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction
D000316:Adrenergic alpha-Agonists; D015220:Calcium Channels; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D010656:Phenylephrine; D004533:Egtazic Acid; D006493:Heparin; D002118:Calcium