Introduction
Catestain, a 21 amino acid fragment of chromogranin A (CgA), is divided into human CgA352-372 and bovine CgA344-364. It is a cationic and hydrophobic peptide formed endogenously by proteolytic cleavage of its precursor CgA. CgA, 48 kDa acidic polypeptide, is the major soluble protein in the core of catecholamine storage vesicles, and as an index member of the chromogranin/secretogranin protein family, CgA is a secretory proprotein that is endoproteolytically processed to give rise to several peptides of biological importance. Catestain is a potent inhibitor of nicotinic cholinergic-stimulated catecholamine secretion.
Biological Activity
Catestain is formed and secreted in chromaffin granules and acts as a nicotinic cholinergic antagonist with characteristic inhibitory effects on nicotinic cationic (Na+, Ca2+) signal transduction. It also blocks nicotinic agonist-induced desensitization of catecholamine release. Catestain specifically inhibits nicotine-induced catecholamine release from chromaffin cells in vitro in a noncompetitive fashion, that is, as a ganglionic blocking agent. It is postulated as important counterregulatory hormones in zero steady-state error homeostasis. According to the research of primary structure and function of the catecholamine release inhibitory peptide catestatin, a core of 15 amino acids (chromogranin A344-358) seems to be sufficient to exert catestatin's typical effects on catecholamine release, nicotinic cationic signal transduction, and blockade of nicotinic agonist-induced desensitization.
Function
Recent studies have documented that the CgA-derived peptide catestatin acts as a novel and potent autocrine modulator of catecholamine secretion in chromaffin cells and adrenergic neurons in isolated cells as well as in intact organisms. Therefore, this endogenous catecholamine-release inhibitory peptide is a logical regulator of blood pressure and cardiac functions. Catestatin also can promote the degranulation of mast cells, regulate autonomic nervous system function, thereby relaxing blood vessels, antagonizing the occurrence of hypertension and promoting the release of basic fibroblast growth factor and activation of mitogen protein kinase by endothelial cells. Information pathway promotes angiogenesis. Catestatin also activates the phosphoinositide-3 kinase/protein kinase B (PI3K/Akt) signaling pathway to antagonize myocardial ischemia-reperfusion injury or delays the course of congestive heart failure by reverse stimulating myocardial beta receptors and other mechanisms.
References:
1. Kennedy, B. P., Mahata, S. K., O'Connor, D. T., & Ziegler, M. G. (1998). Mechanism of cardiovascular actions of the chromogranin A fragment catestatin in vivo. Peptides, 19(7), 1241-1248.
2. Angelone, T., Quintieri, A. M., Brar, B. K., Limchaiyawat, P. T., Tota, B., Mahata, S. K., & Cerra, M. C. (2008). The antihypertensive chromogranin a peptide catestatin acts as a novel endocrine/paracrine modulator of cardiac inotropism and lusitropism. Endocrinology, 149(10), 4780-4793.
3. Mahata, S. K., Mahata, M., Wen, G., Wong, W., Mahapatra, N., Hamilton, B., & O'Connor, D. (2004). The catecholamine release-inhibitory "catestatin" fragment of chromogranin A: naturally occurring human variants with different potencies for multiple chromaffin cell nicotinic cholinergic responses. Molecular pharmacology.
4. Mahata, S. K., Mahata, M., Wakade, A. R., & O'Connor, D. T. (2000). Primary Structure and Function of the Catecholamine Release Inhibitory Peptide Catestatin (Chromogranin A344-364): Identification of Amino Acid Residues Crucial for Activity. Molecular Endocrinology, 14(10), 1525-1535.
5. Mahata, S. K., Mahata, M., Fung, M. M., & O'Connor, D. T. (2010). Reprint of: catestatin: a multifunctional peptide from Chromogranin A. Regulatory peptides, 165(1), 52-62.
