α1-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

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Abstract
.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 in 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 agonist 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 EDTA. 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 .mu.M), 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.

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