Autocrine regulation of parathyroid secretion: inhibition of secretion by chromogranin-A (secretory protein-I) and potentiation of secretion by chromogranin-A and pancreastatin antibodies

• Published in: Endocrinology (Philadelphia) Vol. 127; no. 3; p. 1329
• Main Authors: Fasciotto, B H, Gorr, S U, Bourdeau, A M, Cohn, D V
• Format: Journal Article
• Language: English
• Published: United States 01.09.1990
• Subjects: Animals; Calcium - pharmacology; Cells, Cultured; Chromogranin A; Chromogranins - immunology; Chromogranins - pharmacology; Chromogranins - secretion; Immune Sera - pharmacology; Nerve Tissue Proteins - pharmacology; Pancreatic Hormones - immunology; Pancreatic Hormones - physiology; Parathyroid Glands - drug effects; Parathyroid Glands - secretion; Parathyroid Hormone - secretion; Swine
• ISSN: 0013-7227
• DOI: 10.1210/endo-127-3-1329

Chromogranin-A, also referred to as secretory protein-I, is a 50-kDa protein present in and secreted by most endocrine cells together with the native hormone. Porcine chromogranin-A contains a sequence identical to pancreastatin, suggesting that it is the precursor of pancreastatin. Pancreastatin is a potent inhibitor of parathyroid gland secretion, and it and chromogranin-A inhibit glucose-stimulated insulin release by the pancreas. It is possible that chromogranin-A, pancreastatin, or a related peptide is a physiological inhibitor of secretion by the parathyroid as well as other endocrine glands. As a test of this hypothesis, parathyroid cells in culture were incubated with purified porcine chromogranin-A or antisera to chromogranin-A and pancreastatin. In the absence of exogenous chromogranin-A or antisera, secretion of chromogranin-A and PTH at 0.5 mM Ca2+ was about twice that at 3.0 mM Ca2+. When intact chromogranin-A was added to the incubation medium at 0.5 mM Ca2+, secretion was reduced to the basal level obtained at 3.0 mM Ca2+. Chromogranin-A did not affect the secretion of cells incubated at 3.0 mM Ca2+. At 1 h of incubation, 100 nM chromogranin-A was equivalent in potency to 1 nM pancreastatin, but after 3 h the two agents were equipotent. This suggests that chromogranin-A was processed into biologically active peptide(s) during incubation. Antisera directed against chromogranin-A or pancreastatin potentiated the secretion of both chromogranin-A and PTH at 0.5 mM, but not 3.0 mM, Ca2+. This stimulatory action of the antisera was dose dependent from 1:3200 to 1:400 final dilution, was effective within 2 h, and did not shift the Ca2+ set-point for glandular secretion. These results are consonant with chromogranin-A-derived peptides serving as an autocrine inhibitor of parathyroid gland secretion.