Endocrinology, Vol 135, 337-342, Copyright © 1994 by Endocrine Society

ARTICLES

Inhibition of parathyroid hormone secretion by amino-terminal chromogranin peptides

J Russell, P Gee, SM Liu and RH Angeletti
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.

The parathyroid gland responds to decreases in levels of extracellular calcium by increasing the secretion of both PTH and chromogranin-A (CGA) in approximately equal molar ratios. Because CGA has been suggested to be a precursor for biologically active peptides, we used primary cultures of bovine parathyroid cells to examine the effects of various peptides from CGA as well as analogous peptides from chromogranin-B (CGB) on PTH secretion. In concentrations from 10(-8)- 10(-7) M, amino-terminal peptide CGA-(1-76) effectively inhibited the release of PTH in response to low extracellular calcium. Truncated analogs of this peptide, CGA-(1-40), CGB-(1-41), and CGA-(17-38) were also found to be active in the following order: CGA-(1-76) = CGA-(1-40) = CGB-(1-41) > CGA-(17-38). The biological activity of CGA-(1-40) was markedly reduced after reduction and alkylation, which resulted in disruption of the single disulfide bond between Cys17 and Cys38. Moreover, peptides derived from other regions of CGA and CGB, which included CGA-(403-428), CGB-(1-16), CGB-(316-326), and CGB-(635-657) were inactive. Pulse-chase experiments, using primary cultures of bovine parathyroid cells, revealed the presence of a CGA peptide in the culture medium that had the same amino-terminal sequence and mobility on sodium dodecyl sulfate-polyacrylamide gels as synthetic CGA-(1-76). Furthermore, in binding and cross-linking studies using intact parathyroid cells, CGA-(1-40) formed a single, covalently linked protein complex with a mol wt of 78,000. Formation of the protein complex could be completely inhibited in the presence of an excess of either CGB-(1-41) or CGA-(17-38). These results show that a naturally occurring amino-terminal peptide from CGA as well as shorter analogs can act as potent inhibitors of PTH secretion, and that their biological activity may be mediated through binding to a specific cell surface protein.

This article has been cited by other articles:

				G. M. Schmid, P. Meda, D. Caille, E. Wargent, J. O'Dowd, D. F. Hochstrasser, M. A. Cawthorne, and J.-C. Sanchez Inhibition of Insulin Secretion by Betagranin, an N-terminal Chromogranin A Fragment J. Biol. Chem., April 27, 2007; 282(17): 12717 - 12724. [Abstract] [Full Text] [PDF]

				A. Tanabe, T. Yanagiya, A. Iida, S. Saito, A. Sekine, A. Takahashi, T. Nakamura, T. Tsunoda, S. Kamohara, Y. Nakata, et al. Functional Single-Nucleotide Polymorphisms in the Secretogranin III (SCG3) Gene that Form Secretory Granules with Appetite-Related Neuropeptides Are Associated with Obesity J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1145 - 1154. [Abstract] [Full Text] [PDF]

				L. Taupenot, K. L. Harper, and D. T. O'Connor The Chromogranin-Secretogranin Family N. Engl. J. Med., March 20, 2003; 348(12): 1134 - 1149. [Full Text] [PDF]

				B. Colombo, R. Longhi, C. Marinzi, F. Magni, A. Cattaneo, S. H. Yoo, F. Curnis, and A. Corti Cleavage of Chromogranin A N-terminal Domain by Plasmin Provides a New Mechanism for Regulating Cell Adhesion J. Biol. Chem., November 22, 2002; 277(48): 45911 - 45919. [Abstract] [Full Text] [PDF]

				B. Colombo, F. Curnis, C. Foglieni, A. Monno, G. Arrigoni, and A. Corti Chromogranin A Expression in Neoplastic Cells Affects Tumor Growth and Morphogenesis in Mouse Models Cancer Res., February 1, 2002; 62(3): 941 - 946. [Abstract] [Full Text] [PDF]

				V. Turquier, H. Vaudry, S. Jégou, and Y. Anouar Frog Chromogranin A Messenger Ribonucleic Acid Encodes Three Highly Conserved Peptides. Coordinate Regulation of Proopiomelanocortin and Chromogranin A Gene Expression in the Pars Intermedia of the Pituitary During Background Color Adaptation Endocrinology, September 1, 1999; 140(9): 4104 - 4112. [Abstract] [Full Text]

				E. Soliman, L. Canaff, J. Fox, and G. N. Hendy In Vivo Regulation of Chromogranin A Messenger Ribonucleic Acid in the Parathyroid by 1,25-Dihydroxyvitamin D: Studies in Normal Rats and in Chronic Renal Insufficiency Endocrinology, June 1, 1997; 138(6): 2596 - 2600. [Abstract] [Full Text] [PDF]

				S. Ratti, F. Curnis, R. Longhi, B. Colombo, A. Gasparri, F. Magni, E. Manera, M.-H. Metz-Boutigue, and A. Corti Structure-Activity Relationships of Chromogranin A in Cell Adhesion. IDENTIFICATION OF AN ADHESION SITE FOR FIBROBLASTS AND SMOOTH MUSCLE CELLS J. Biol. Chem., September 15, 2000; 275(38): 29257 - 29263. [Abstract] [Full Text] [PDF]

				K. Lugardon, S. Chasserot-Golaz, A.-E. Kieffer, R. Maget-Dana, G. Nullans, B. Kieffer, D. Aunis, and M.-H. Metz-Boutigue Structural and Biological Characterization of Chromofungin, the Antifungal Chromogranin A-(47-66)-derived Peptide J. Biol. Chem., September 14, 2001; 276(38): 35875 - 35882. [Abstract] [Full Text] [PDF]