Chromostatin inhibits catecholamine secretion in adrenal chromaffin cells by activating a protein phosphatase.
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.
Galindo
E
E
Institut National de la Santé et de la Recherche Médicale, U-338, Biologie de la Communication Cellulaire, Strasbourg, France.
Zwiller
J
J
Bader
M F
MF
Aunis
D
D
D000313:Adrenal Medulla / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D053379:Chromogranin A; D002864:Chromogranins / Q000494:pharmacology*; D004789:Enzyme Activation; D004988:Ethers, Cyclic / Q000494:pharmacology; D007700:Kinetics; D007832:Lasalocid / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D019319:Okadaic Acid; D010446:Peptide Fragments / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats
D053379:Chromogranin A; D002864:Chromogranins; D004988:Ethers, Cyclic; D010446:Peptide Fragments; C067412:chromostatin; D019319:Okadaic Acid; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D002118:Calcium; D007832:Lasalocid; D009638:Norepinephrine