Autocrine regulation of parathyroid secretion: inhibition of secretion by chromogranin-A (secretory protein-I) and potentiation of secretion by chromogranin-A and pancreastatin antibodies.
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.
Fasciotto
B H
BH
Department of Oral Health, University of Louisville Schools of Dentistry and Medicine, Kentucky 40292.
Gorr
S U
SU
Bourdeau
A M
AM
Cohn
D V
DV
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D053379:Chromogranin A; D002864:Chromogranins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D007106:Immune Sera / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D010187:Pancreatic Hormones / Q000276:immunology* / Q000502:physiology; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism; D013552:Swine
D053379:Chromogranin A; D002864:Chromogranins; D007106:Immune Sera; D009419:Nerve Tissue Proteins; D010187:Pancreatic Hormones; D010281:Parathyroid Hormone; C050836:pancreastatin; D002118:Calcium