Protein kinase C is involved in adrenergic stimulation of pineal cGMP accumulation.
The amounts of cAMP and cGMP in the rat pinealocyte are regulated by norepinephrine acting through synergistic dual receptor mechanisms involving alpha 1- and beta-adrenoceptors (Vanecek, J., Sugden, D., Weller, J.L., and Klein, D.C. (1985) Endocrinology 116, 2167-2173; Sugden, L., Sugden, D., and Klein, D.C. (1986) J. Biol. Chem. 261, 11608-11612). Based on the available evidence, it appears that Ca2+-phospholipid-dependent protein kinase is involved in the alpha 1-adrenergic potentiation of beta-adrenergic stimulation of cAMP, but not in the stimulation of cGMP (Sugden, D., Vanecek, J., Klein, D.C., Thomas, T.P., and Anderson, W.B. (1985) Nature 314, 359-361). In the present study the role of protein kinase C in the adrenergic stimulation of cGMP was reinvestigated, with the purpose of determining whether protein kinase C activators would potentiate the effects of beta-adrenergic agonists on cGMP if cells were also treated with agents known to elevate intracellular free Ca2+. The protein kinase C activator 4 beta-phorbol 12-myristate 13-acetate (PMA) markedly elevated the cGMP content of beta-adrenergically stimulated pinealocytes which had also been treated with 1 microM A23187, 15 mM K+, or 1 microM ouabain. The effects of A23187 were blocked by EGTA and those of K+ were blocked by nifedipine, establishing the involvement of Ca2+. The stimulatory effects of PMA on cGMP accumulation were mimicked by other protein kinase C activators. PMA also stimulated cGMP accumulation in cells treated with cholera toxin (1 microgram/ml) and A23187 (1 microM), but not in cells treated only with cholera toxin. These results suggest that protein kinase C, which is activated in the pinealocyte by the alpha-adrenergic agonist phenylephrine, is probably involved in the adrenergic regulation of cGMP accumulation at a step distal to receptor activation.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D000001:Calcimycin; D010042:Ouabain; D000242:Cyclic AMP; D011493:Protein Kinase C; D006152:Cyclic GMP; D009543:Nifedipine; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium