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

• Published in: The Journal of biological chemistry 1987-05, Vol.262 (15), p.6947-6950
• Main Authors: Galizzi, J P, Qar, J, Fosset, M, Van Renterghem, C, Lazdunski, M
• Format: Article
• Language: English
• Subjects: Animals; Aorta; Arginine Vasopressin - pharmacology; Biological and medical sciences; Bombesin - pharmacology; calcium; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Cell Line; Cell physiology; Cyclic AMP - physiology; Diglycerides - pharmacology; Enzyme Activation - drug effects; Fundamental and applied biological sciences. Psychology; Hormonal regulation; Ion Channels - drug effects; Ion Channels - physiology; Isradipine; Kinetics; Molecular and cellular biology; Muscle, Smooth, Vascular - physiology; Oxadiazoles - pharmacology; Oxytocin - pharmacology; peptide hormones; Phorbol Esters - pharmacology; Phosphatidylinositols - metabolism; protein kinase C; Protein Kinase C - metabolism; Rats
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)48182-3

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.