Pancreastatin, a presumed product of chromogranin-A (secretory protein-I) processing, inhibits secretion from porcine parathyroid cells in culture.
Chromogranin-A, also referred to as secretory protein-I, is a 50K protein found in and secreted by endocrine cells, in which it is costored with the native hormone. Porcine chromogranin-A contains a sequence identical to pancreastatin, a 49-amino acid, C-terminally amidated peptide that has been isolated from porcine pancreas, suggesting that chromogranin-A is the precursor of pancreastatin. Pancreastatin has been found to be a potent inhibitor of glucose-stimulated insulin release. As it is possible that pancreastatin inhibits secretion from other chromogranin-A-containing tissues in which it may be formed, we tested its action on dispersed porcine parathyroid cells in culture. Secretion of chromogranin-A and PTH was up to 6-fold greater at 0.5 mM Ca2+ than at 3.0 mM Ca2+. Pancreastatin (1 nM) reduced the secretion of both chromogranin-A and PTH at 0.5 mM Ca2+ to approximately the levels found at 3.0 mM Ca2+, but did not affect secretion at 3.0 mM Ca2+. Pancreastatin (0.01-1.0 nM) inhibited secretion of chromogranin-A in a dose-dependent fashion. Preincubation of the cells with pancreastatin was not required for inhibition. Transfer of inhibited cells to medium without pancreastatin led to restoration of secretion within 90 min. Phorbol myristate acetate (1.6 microM) stimulated secretion of PTH and chromogranin-A at 3.0 mM Ca2+, but not at 0.5 mM Ca2+. Pancreastatin reversed this stimulation, demonstrating that its inhibition was independent of Ca2+ concentration. These results are consonant with pancreastatin playing a physiological role in modulation of secretion by the parathyroid and, by extension, other endocrine tissues.
Fasciotto
B H
BH
Department of Oral Health, University of Louisville, Kentucky 40292.
Gorr
S U
SU
DeFranco
D J
DJ
Levine
M A
MA
Cohn
D V
DV
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D053379:Chromogranin A; D002864:Chromogranins / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010187:Pancreatic Hormones / Q000494:pharmacology*; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D053379:Chromogranin A; D002864:Chromogranins; D009419:Nerve Tissue Proteins; D010187:Pancreatic Hormones; D010281:Parathyroid Hormone; C050836:pancreastatin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium