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

Brigitte H. Fasciotto, Sven Ulrik Gorr, Agnes M. Bourdeau, David V. Cohn

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1329-1335
Number of pages7
JournalEndocrinology
Volume127
Issue number3
DOIs
StatePublished - Jan 1 1990

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