Halothane and octanol block Ca2+ oscillations in pancreatic acini by multiple mechanisms.
This study has investigated halothane and octanol, reported inhibitors of gap junction permeability, for their effects on acinar cell intracellular Ca2+ concentration ([Ca2+]i) signaling. Halothane and octanol alone at maximal concentrations induced a sustained rise in [Ca2+]i of 23 +/- 4 and 29 +/- 5 nM, respectively. Cholecystokinin (CCK, 20 pM) induced [Ca2+]i oscillations in single acinar cells within the acinus to a peak of 275 +/- 17 nM, rising from a basal level of 55 +/- 3 nM. These oscillations were completely abolished by superfusion with both halothane (4 mM) and octanol (1 mM), concentrations that blocked the spread of Lucifer yellow from cell to cell within an acinus. Lower concentrations of octanol markedly reduced the oscillation frequency (0.2 and 0.5 mM octanol: reduction in oscillation frequency of 69 +/- 6 and 43 +/- 6%, respectively). These agents however, over the same concentration range, also exhibited similar inhibitory effects on [Ca2+]i oscillations in single cells dispersed from the acinus (reduction in oscillation frequency of 75 +/- 10 and 32 +/- 12% for 0.2 and 0.5 mM octanol, respectively), suggesting additional effects other than on gap junctions. Halothane inhibited inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] production in response to both 1 and 10 nM CCK (31 and 40% inhibition, respectively), possibly explaining its effects on [Ca2+]i oscillations, whereas octanol showed no significant inhibition. Octanol, unlike halothane, blocked Ins(1,4,5)P3-induced Ca2+ release from permeabilized acini, an effect that was most pronounced at a more physiological Ins(1,4,5)P3 concentration. Octanol did not affect Ins(1,4,5)P3 binding to Ins(1,4,5)P3 receptor preparation. In conclusion, although halothane and octanol block gap junction permeability in pancreatic acinar cells, these agents also affect Ins(1,4,5)P3 production and Ca2+ mobilization in response to agonist stimulation.
D020003:1-Octanol; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D005456:Fluorescent Dyes; D006221:Halothane / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007546:Isoquinolines; D008297:Male; D000442:Octanols / Q000494:pharmacology*; D009991:Oscillometry; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism
D015220:Calcium Channels; D005456:Fluorescent Dyes; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007546:Isoquinolines; D000442:Octanols; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; C017475:lucifer yellow; D020003:1-Octanol; D002118:Calcium; D006221:Halothane