CALCITONIN GENE-RELATED PEPTIDE STIMULATES INTRACELLULAR CAMP VIA A PROTEIN KINASE-C-CONTROLLED MECHANISM IN HUMAN OCULAR CILIARY EPITHELIAL-CELLS

Calcitonin gene-related peptides I and II (CGRP I and II) were found to stimulate cAMP levels by ∼4-6 fold in human nonpigmented ciliary epithelial cells with half-maximal effective concentrations of 20×1010 and 3×10-10M, respectively. Prior exposure of cells to 6×10-7M phorbol 12-myristate, 13-acetate for 15 min resulted in a 40-50% inhibition of CGRP II-dependent cAMP stimulation. Phorbol didecanoate and dioctanyolglycerol also effectively inhibited, whereas 4c phorbol didecanoate, an ineffective activator of protein kinase C, had no effect. Staurosporine, a protein kinase C inhibitor, blocked the inhibition of cAMP formation by phorbol esters. cAMP stimulation by forskolin or cholera toxin was not inhibited by phorbol esters, suggesting that neither a GS protein nor adenylyl cyclase is the site of inhibition by protein kinase C. These data therefore suggest that CGRP receptors are required for inhibition of adenylate cyclase by protein kinase C. © 1992.