PMID- 8072853 OWN - NLM STAT- MEDLINE DCOM- 19940926 LR - 20191210 IS - 0031-6768 (Print) IS - 0031-6768 (Linking) VI - 427 IP - 3-4 DP - 1994 Jun TI - The thapsigargin-evoked increase in [Ca2+]i involves an InsP3-dependent Ca2+ release process in pancreatic acinar cells. PG - 325-31 AB - In pancreatic acinar cells, as in many other cell types, the tumour promoter thapsigargin (TG) evokes a significant increase of intracellular free Ca2+ ([Ca2+]i). The increases of [Ca2+]i evoked by TG was associated with significant changes of plasma membrane Ca2+ permeability, with [Ca2+]i values following changes in extracellular [Ca2+]. Plasma membrane Ca2+ extrusion is activated rapidly as a consequence of the rise in [Ca2+]i evoked by TG and the rate of extrusion is linearly dependent on [Ca2+]i up to 1 microM Ca2+. In contrast, the activation of the Ca2+ entry pathway is delayed and the apparent rate of Ca2+ entry is independent of [Ca2+]i. In the presence of 20 mM caffeine, which reduces the resting levels of inositol trisphosphate (InsP3), the increase of [Ca2+]i evoked by TG was significantly reduced. The reduction was manifest both as a decrease of the amplitude of the [Ca2+]i peak (30% reduction) and, more importantly, as a reduction of the apparent maximal rate of [Ca2+]i increase (from 12.3 +/- 1.0 to 6.1 +/- 0.6 nM Ca2+/s). The inhibition evoked by caffeine was reversible and the removal of caffeine in the continuous presence of TG evoked a further increase of [Ca2+]i. The amplitude of the [Ca2+]i increase upon caffeine removal was reduced as a function of the time of TG exposure. Addition of TG in the presence of 1 mM La3+, which is known to inhibit the plasma membrane Ca(2+)-activated adenosine triphosphatase, induced a much higher peak of [Ca2+]i. This increase was associated with an augmentation of the apparent rate of [Ca2+]i increase (from 12.3 +/- 1.2 to 16.1 +/- 1.9 nM Ca2+/s).(ABSTRACT TRUNCATED AT 250 WORDS) FAU - Toescu, E C AU - Toescu EC AD - Physiological Laboratory, Liverpool University, Merseyside, UK. FAU - Petersen, O H AU - Petersen OH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Pflugers Arch JT - Pflugers Archiv : European journal of physiology JID - 0154720 RN - 0 (Terpenes) RN - 3G6A5W338E (Caffeine) RN - 67526-95-8 (Thapsigargin) RN - 6I3K30563S (Lanthanum) RN - 85166-31-0 (Inositol 1,4,5-Trisphosphate) RN - EC 7.2.2.10 (Calcium-Transporting ATPases) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Caffeine/pharmacology MH - Calcium/*metabolism MH - Calcium-Transporting ATPases/antagonists & inhibitors MH - Cell Membrane/metabolism MH - In Vitro Techniques MH - Inositol 1,4,5-Trisphosphate/*physiology MH - Ion Transport/drug effects MH - Lanthanum/physiology MH - Mice MH - Pancreas/cytology/*metabolism MH - Terpenes/*pharmacology MH - Thapsigargin EDAT- 1994/06/01 00:00 MHDA- 1994/06/01 00:01 CRDT- 1994/06/01 00:00 PHST- 1994/06/01 00:00 [pubmed] PHST- 1994/06/01 00:01 [medline] PHST- 1994/06/01 00:00 [entrez] AID - 10.1007/BF00374541 [doi] PST - ppublish SO - Pflugers Arch. 1994 Jun;427(3-4):325-31. doi: 10.1007/BF00374541.