Catecholamine secretory vesicle core proteins (chromogranins) contain an activity that inhibits catecholamine release, but the identity of the responsible peptide has been elusive. Size-fractionated chromogranins antagonized nicotinic cholinergic-stimulated catecholamine secretion; the inhibitor was enriched in processed chromogranin fragments, and was liberated from purified chromogranin A. Of 15 synthetic peptides spanning ~ 80% of chromogranin A, one (bovine chromogranin A(344-364) [RSMRLSFRARGYGFRGPGLQL], or catestatin) was a potent, dose-dependent (IC50 ~ 200 nM), reversible secretory inhibitor on pheochromocytoma and adrenal chromaffin cells, as well as noradrenergic neurites. An antibody directed against this peptide blocked the inhibitory effect of chromogranin A proteolytic fragments on nicotinic- stimulated catecholamine secretion. This region of chromogranin A is extensively processed within chromaffin vesicles in vivo. The inhibitory effect was specific for nicotinic cholinergic stimulation of catecholamine release, and was shared by this chromogranin A region from several species. Nicotinic cationic (Na+, Ca2+) signal transduction was specifically disrupted by catestatin. Even high-dose nicotine failed to overcome the inhibition, suggesting noncompetitive nicotinic antagonism. This small domain within chromogranin A may contribute to a novel, autocrine, homeostatic (negative-feedback) mechanism controlling catecholamine release from chromaffin cells and neurons.
CITATION STYLE
Mahata, S. K., O’Connor, D. T., Mahata, M., Yoo, S. H., Taupenot, L., Wu, H., … Parmer, R. J. (1997). Novel autocrine feedback control of catecholamine release: A discrete chromogranin A fragment is a noncompetitive nicotinic cholinergic antagonist. Journal of Clinical Investigation, 100(6), 1623–1633. https://doi.org/10.1172/JCI119686
Mendeley helps you to discover research relevant for your work.