Differential involvement of phospholipase A2/arachidonic acid and phospholipase C/phosphoinositol pathways during cholecystokinin receptor activated Ca2+ oscillations in pancreatic acini.
In pancreatic acini, administration of the phospholipase C inhibitor, U-73122, abolished Ca2+ oscillations and amylase secretion induced by CCK but had much less effect on the action of CCK analog JMV-180. In contrast, the phospholipase A2 inhibitor, ONO-RS-082, inhibited both Ca2+ spikes and amylase secretion induced by JMV-180, but it had little effect on the action of CCK-8. Both arachidonic acid (AA) and a cytochrome P-450 inhibitor, SKF-96365, generated Ca2+ spikes from the agonist-sensitive pool. AA was capable of releasing Ca2+ from the endoplasmic reticulum (ER), suggesting the direct Ca2+ releasing pathway. There is no evidence of Ca(2+)-induced Ca2+ release (CICR) since neither caffeine, a CICR potentiator, nor ryanodine, a CICR inhibitor, modulated agonist-induced Ca2+ oscillations and Ca2+ release from the ER. On the contrary, increasing concentrations of caffeine abolished agonist-induced Ca2+ spikes. Therefore we have demonstrated that depending on the agonists used, CCK receptor activation may result in the differential involvement of the phosphoinositol and arachidonic acid pathways to mediate calcium oscillation and amylase secretion.
Tsunoda
Y
Y
Department of Internal Medicine, University of Michigan, Ann Arbor 48109.
Owyang
C
C
D062365:Aminobenzoates / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002723:Chlorobenzoates; D002934:Cinnamates / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D010507:Periodicity; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D054467:Phospholipases A2; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D012433:Ryanodine / Q000494:pharmacology; D015398:Signal Transduction; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D062367:ortho-Aminobenzoates
D062365:Aminobenzoates; D002723:Chlorobenzoates; D002934:Cinnamates; D004963:Estrenes; D007093:Imidazoles; D011760:Pyrrolidinones; D011949:Receptors, Cholecystokinin; D062367:ortho-Aminobenzoates; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C058451:JMV 180; D012433:Ryanodine; D016718:Arachidonic Acid; D015544:Inositol 1,4,5-Trisphosphate; C060048:2-(4-amylcinnamoyl)amino-4-chlorobenzoic acid; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D000681:Amylases; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D012844:Sincalide; D002118:Calcium