Effects of phospholipase C inhibitors on Ca2+ channel stimulation and Ca2+ release from intracellular stores evoked by alpha 1A- and alpha 2A-adrenoceptors in rat portal vein myocytes.
The ability of phospholipase C inhibitors to inhibit Ca2+ channel stimulation and Ca2+ release from intracellular stores evoked by norepinephrine in single rat portal vein myocytes was investigated in the aim of identifying the type of phospholipase C involved in the transduction pathways activated by alpha 1A- and alpha 2A-adrenoceptors. U73122 (an inhibitor of phosphatidylinositol-phospholipase C) inhibited in a concentration-dependent manner the release of Ca2+ from the intracellular stores induced by activation of alpha 1A-adrenoceptors and related to inositol phosphate production whereas U73343 was ineffective. Both compounds had no effect on the release of Ca2+ induced by caffeine. However, U73122 and U73343 inhibited the L-type Ca2+ channel. D609 (an inhibitor of phosphatidylcholine-phospholipase C) had no direct inhibitory effects on the L-type Ca2+ channel but it inhibited concentration dependently the alpha 2A-adrenoceptor-induced stimulation of Ca2+ channels, which had been shown to be independent of phosphatidylinositol hydrolysis. Therefore, these results suggest that alpha 2A-adrenoceptors activate a phosphatidylcholine-phospholipase C in vascular myocytes. However, D609 had other sites of action as it blocked norepinephrine- and caffeine-induced Ca2+ release from the intracellular stores.
Macrez-Leprêtre
N
N
Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, URA CNRS 1489, Université de Bordeaux II, France.
Morel
J L
JL
Mironneau
J
J
D000818:Animals; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004963:Estrenes / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009636:Norbornanes; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D001952:Bridged-Ring Compounds; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D004963:Estrenes; D009636:Norbornanes; D011760:Pyrrolidinones; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D013859:Thiocarbamates; D013871:Thiones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C074854:U 73343; C046498:tricyclodecane-9-yl-xanthogenate; D010738:Type C Phospholipases; D002118:Calcium; D009638:Norepinephrine