PMID- 7508754 OWN - NLM STAT- MEDLINE DCOM- 19940321 LR - 20191210 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1220 IP - 2 DP - 1994 Jan 13 TI - Effect of inhibition of microsomal Ca(2+)-ATPase on cytoplasmic calcium and enzyme secretion in pancreatic acini. PG - 199-208 AB - We used thapsigargin (TG), 2,5-di-tert-butyl-1,4-benzohydroquinone (BHQ) and cyclopiazonic acid (CPA), each of which inhibits microsomal Ca(2+)-ATPase, to evaluate the effects of this inhibition on cytoplasmic free calcium ([Ca2+]i) and secretagogue-stimulated enzyme secretion in rat pancreatic acini. Using single-cell microspectrofluorimetry of fura-2-loaded acini we found that all three agents caused a sustained increase in [Ca2+]i by mobilizing calcium from inositol-(1,4,5)-trisphosphate-sensitive intracellular calcium stores and by promoting influx of extracellular calcium. Concentrations of all three agents that increased [Ca2+]i potentiated the stimulation of enzyme secretion caused by secretagogues that activate adenylate cyclase but inhibited the stimulation of enzyme secretion caused by secretagogues that activate phospholipase C. With BHQ, potentiation of adenylate cyclase-mediated enzyme secretion occurred immediately whereas inhibition of phospholipase C-mediated enzyme secretion occurred only after several min of incubation. In addition, the effects of BHQ and CPA on both [Ca2+]i and secretagogue-stimulated enzyme secretion were reversed completely by washing whereas the actions of TG could not be reversed by washing. Concentrations of BHQ in excess of those that caused maximal changes in [Ca2+]i inhibited all modes of stimulated enzyme secretion by a mechanism that was apparently unrelated to changes in [Ca2+]i. Finally, in contrast to the findings with TG and BHQ, CPA inhibited bombesin-stimulated enzyme secretion over a range of concentrations that was at least 10-fold lower than the range of concentrations over which CPA potentiated VIP-stimulated enzyme secretion. FAU - Metz, D C AU - Metz DC AD - Digestive Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892. FAU - Pradhan, T K AU - Pradhan TK FAU - Mrozinski, J E Jr AU - Mrozinski JE Jr FAU - Jensen, R T AU - Jensen RT FAU - Turner, R J AU - Turner RJ FAU - Patto, R J AU - Patto RJ FAU - Gardner, J D AU - Gardner JD LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (Hydroquinones) RN - 0 (Indoles) RN - 26XK13B61B (2,5-di-tert-butylhydroquinone) RN - EC 3.2.1.- (Amylases) RN - EC 7.2.2.10 (Calcium-Transporting ATPases) RN - M03GIQ7Z6P (Sincalide) RN - SY7Q814VUP (Calcium) RN - X9TLY4580Z (cyclopiazonic acid) SB - IM MH - Amylases/*metabolism MH - Animals MH - Calcium/*metabolism MH - Calcium-Transporting ATPases/*antagonists & inhibitors MH - Cytoplasm/metabolism MH - Hydroquinones/pharmacology MH - Indoles/pharmacology MH - Male MH - Microsomes/enzymology MH - Pancreas/*metabolism/ultrastructure MH - Rats MH - Rats, Sprague-Dawley MH - Sincalide/pharmacology EDAT- 1994/01/13 00:00 MHDA- 2001/03/28 10:01 CRDT- 1994/01/13 00:00 PHST- 1994/01/13 00:00 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1994/01/13 00:00 [entrez] AID - 0167-4889(94)90136-8 [pii] AID - 10.1016/0167-4889(94)90136-8 [doi] PST - ppublish SO - Biochim Biophys Acta. 1994 Jan 13;1220(2):199-208. doi: 10.1016/0167-4889(94)90136-8.