Inhibitors of cellular proteolysis cause increased secretion from parathyroid cells.
The secretion but not the biosynthesis of parathyroid hormone and secretory protein 1 is strongly, negatively regulated by extracellular [Ca2+]. In order to examine the hypothesis that decreased degradation might directly cause increased secretion, we tested the effects of agents that suppress cellular degradation via different mechanisms: 3-methyladenine, chloroquine, and 1-deoxynojirimycin. When secretion was inhibited by high [Ca2+], all agents caused increased secretion, but at low [Ca2+] only deoxynojirimycin was effective. Results derived from the use of two radioimmunoassays for parathyroid hormone suggested that the increased secretion was due to reduced destruction of secretory vesicles by lysosomes, and to reduced proteolysis of their contents by secretory vesicle proteases.
MacGregor
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RR
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City 66103.
Bansal
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DD
D017485:1-Deoxynojirimycin; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D053379:Chromogranin A; D002864:Chromogranins; D005089:Exocytosis / Q000187:drug effects; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011863:Radioimmunoassay
D002135:Calcium-Binding Proteins; D053379:Chromogranin A; D002864:Chromogranins; D010281:Parathyroid Hormone; D011480:Protease Inhibitors; D017485:1-Deoxynojirimycin; C025946:3-methyladenine; D002738:Chloroquine; D000225:Adenine; D005944:Glucosamine; D002118:Calcium