Alpha 1-adrenergic potentiation of vasoactive intestinal peptide stimulation of rat pinealocyte adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate: evidence for a role of calcium and protein kinase-C.
alpha 1-Adrenergic agonists have recently been found to potentiate vasoactive intestinal peptide (VIP) stimulation of rat pinealocyte cAMP and cGMP. alpha 1-Adrenergic agonists also elevate pineal intracellular Ca2+ [( Ca2+]i) and activate protein kinase-C. In the present study, the possible involvement of Ca2+ and protein kinase-C in the alpha 1-adrenergic potentiation of VIP-stimulated cAMP and cGMP accumulation was examined with agents that alter [Ca2+]i or activate protein kinase-C. It was found that treatment with a Ca2+ chelator or with inorganic Ca2+ channel blockers inhibited alpha 1-adrenergic potentiation of VIP-stimulated cAMP and cGMP responses. Increasing [Ca2+]i by treatment with A23187, ouabain, or K+ potentiated VIP stimulation of cAMP and cGMP response. These observations indicate that Ca2+ mediates the alpha 1-adrenergic potentiation of VIP-stimulated cAMP and cGMP accumulation, as is true for the alpha 1-adrenergic potentiation of beta-adrenergic stimulated cAMP and cGMP accumulation. Activators of protein kinase-C mimicked the large effect alpha 1-adrenergic agonists have on cAMP accumulation in VIP-treated pinealocytes and had a small effect on cGMP accumulation in VIP-treated cells. These effects were not blocked by the Ca2+ chelator EGTA. However, the effects of a protein kinase-C activator on the cGMP response in VIP-stimulated cells were amplified by K+ (15 mM) or ouabain (1 microM), presumably through an action causing an increase in [Ca2+]i. These results suggest protein kinase-C is involved in the alpha 1-adrenergic potentiation of VIP-stimulated cAMP accumulation, as is the case for the alpha 1-adrenergic potentiation of beta-adrenergic stimulated cAMP. Protein kinase-C is also involved in cGMP accumulation, provided that there is a modest increase in [Ca2+]i.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / 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; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D014660:Vasoactive Intestinal Peptide; D000001:Calcimycin; D010042:Ouabain; D000242:Cyclic AMP; D011493:Protein Kinase C; D006152:Cyclic GMP; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine