title: Regulation of calcium channels in aortic muscle cells by protein kinase C activators (diacylglycerol and phorbol esters) and by peptides (vasopressin and bombesin) that stimulate phosphoinositide breakdown.
abstract: Voltage-dependent Ca2+ channels of the aortic cell line A7r5 were studied using 45Ca2+ flux experiments. Ca2+ channels which have been studied belong to the L-type and are very sensitive to inhibitors and activators in the 1,4-dihydropyridine series as well as to (-)desmethoxyverapamil and d-cis-diltiazem. L-type Ca2+ channels in these smooth muscle cells are not affected by cyclic 8-bromo-AMP and dibutyryl cyclic AMP. However, the activity of these channels is strongly depressed after treatment with diacylglycerols (1-oleyl 2-acetylglycerol and 1,2-dioctanoylglycerol). Phorbol esters, which like diacylglycerols are well-known activators of protein kinase C (the Ca2+- and phospholipid-dependent enzyme), inhibit 70% of Ca2+ channel activity (K0.5 = 25 nM for phorbol 12-myristate 13-acetate and K0.5 = 200 nM for phorbol 12,13-dibutyrate). Phorbol esters that are inactive on kinase C are without effect on Ca2+ channel activity. [Arg8]Vasopressin and bombesin, two peptides that are well known for their action on polyphosphoinositide metabolism, inhibit Ca2+ channel activity to the same extent as active phorbol esters (65-70%). Oxytocin has the same type of effect presumably by acting at the V1-receptor. Both effects of [Arg8]vasopressin and oxytocin are suppressed by [1-(beta-mercapto-beta,beta-diethylpropionic acid)4-valine]arginine vasopressin, a specific vasopressin antagonist at the V1-receptor.
mesh_terms: D000818:Animals; D001011:Aorta; D001127:Arginine Vasopressin / Q000494:pharmacology; D001839:Bombesin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D017275:Isradipine; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010069:Oxadiazoles / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats
chemical_list: D002121:Calcium Channel Blockers; D004075:Diglycerides; D007473:Ion Channels; D010069:Oxadiazoles; D010703:Phorbol Esters; D010716:Phosphatidylinositols; D001127:Arginine Vasopressin; D010121:Oxytocin; D000242:Cyclic AMP; D011493:Protein Kinase C; D001839:Bombesin; D002118:Calcium; D017275:Isradipine