okadaic-acid and chromostatin

Chromostatin is a 20-residue peptide derived from chromogranin A (CGA), the major soluble component of secretory granules in adrenal medullary chromaffin cells. One known biological function of chromostatin is to inhibit the secretagogue-evoked catecholamine secretion from chromaffin cells. Putative receptors are present on the chromaffin-cell plasma membrane, and the activation of such receptors leads to the inhibition of L-type voltage-sensitive calcium channels. We report here that exposure of chromaffin cells to chromostatin modifies neither cAMP and cGMP levels nor protein kinase C activity but does provoke the activation of soluble protein phosphatase (PPase) type 2A in a dose-dependent manner compatible with the peptide concentration inhibiting catecholamine secretion. The activation of the PPase as well as the inhibition of both secretagogue-induced Ca2+ entry and catecholamine secretion by chromostatin were all blocked by okadaic acid, a specific PPase inhibitor. We suggest that chromostatin directly or indirectly stimulates PPase-2A, dephosphorylating a target protein and lowering its activity in the secretory process.

Topics: Adrenal Medulla; Animals; Calcium; Cattle; Cells, Cultured; Chromogranin A; Chromogranins; Enzyme Activation; Ethers, Cyclic; Kinetics; Lasalocid; Norepinephrine; Okadaic Acid; Peptide Fragments; Phosphoprotein Phosphatases; Protein Kinase C; Rats