Intracellular control of IP3-independent Ca2+ oscillations in pancreatic acini.
In pancreatic acini, the high affinity cholecystokinin (CCK) receptor agonist, CCK-OPE which utilizes the phospholipase A2 (PLA2)/arachidonic acid (AA) pathway, dose-dependently increased intracellular Ca2+ spike frequency and amplitude. An uncoupler of proton gradients, FCCP, abolished Ca2+ oscillations and amylase secretion induced by CCK-OPE. Furthermore, FCCP or decreasing extravesicular pH inhibited ATP-dependent 45Ca2+ uptake into the endoplasmic reticulum (ER) fraction. On the other hand, cytosolic acidification induced by Na(+)-free medium led to Ca2+ oscillations. Depletion of intracellular ATP by antimycin resulted in an abolition of the response to CCK-OPE. Administration of the K+ ionophore, valinomycin, abolished the action of CCK-OPE. Decreasing K+ concentrations outside the ER vesicles inhibited ATP-dependent 45Ca2+ uptake and AA-induced 45Ca2+ release. Caffeine inhibited the actions of CCK-OPE, whereas ryanodine did not have any effects. These data suggest that IP3-independent Ca2+ oscillations mediated by the PLA2 cascades involve the release of intracellular Ca2+ by AA and reuptake of Ca2+ by an ATP-dependent Ca2+/H+ antiport. Furthermore, the presence of K+ membrane potential gradient across the ER membrane is required for normal Ca2+ oscillations.
Tsunoda
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Y
Department of Internal Medicine, University of Michigan, Ann Arbor 48109, USA.
Yoshida
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H
Owyang
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C
D000255:Adenosine Triphosphate / Q000378:metabolism; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D000968:Antimycin A / Q000031:analogs & derivatives / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000502:physiology; D012433:Ryanodine / Q000494:pharmacology; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology; D014634:Valinomycin / Q000494:pharmacology
D010446:Peptide Fragments; D011949:Receptors, Cholecystokinin; D014475:Uncoupling Agents; C032456:antimycin; C067408:cholecystokinin (26-32), Tyr-Gly-Nle(28,31) phenethyl ester-; D012433:Ryanodine; D014634:Valinomycin; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D002110:Caffeine; D000968:Antimycin A; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D000681:Amylases; D012844:Sincalide; D011188:Potassium; D002118:Calcium