Characteristics of phosphoinositide-specific phospholipase C activity from mouse pancreatic islets.
In pancreatic islets the bulk of phosphoinositide-specific phospholipase C (PI-PLC) activity was cytosolic. The soluble enzyme was activated by submicromolar concentrations of Ca2+, independent of calmodulin. It was unaffected by glucose and a series of glycolytic intermediates, including glyceraldehyde 3-phosphate. These observations lend support to the hypothesis that glucose-stimulated inositol triphosphate production in islets may be secondary to and provoked by glucose-mediated Ca2+ influx. All four pyridine nucleotides stimulated PI-PLC. Phosphatidylinositol hydrolysis was also stimulated by dioleine and arachidonic acid, and by the polyamines, putrescine and spermine. Phosphatidylinositol hydrolysis was inhibited by chlorpromazine, tetracaine, ATP, 5'-AMP, inorganic pyrophosphate and by phosphatidylinositol 4,5-bisphosphate, phosphatidylcholine and phosphatidylserine--but not affected by phosphatidylethanolamine. The cyclic nucleotides, cAMP and cGMP had no effect on the enzyme, and GTP-gamma-S did not activate the enzyme event at very low Ca2+ concentrations. The diglyceride lipase inhibitor, RHC 80267, and the cyclooxygenase inhibitor, indomethacin, had no effect on PI-PLC activity.
Hedeskov
C J
CJ
Department of Biochemistry A, Panum Institute, University of Copenhagen, Denmark.
Thams
P
P
Gembal
M
M
Malik
T
T
Capito
K
K
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D000242:Cyclic AMP; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D005986:Glyceraldehyde 3-Phosphate / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000201:enzymology*; D008297:Male; D051379:Mice; D010716:Phosphatidylinositols / Q000378:metabolism*; D011700:Putrescine / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D013379:Substrate Specificity; D013748:Tetracaine / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
D010716:Phosphatidylinositols; D013748:Tetracaine; D005986:Glyceraldehyde 3-Phosphate; D016718:Arachidonic Acid; D013096:Spermine; D000242:Cyclic AMP; D010738:Type C Phospholipases; D011796:Quinacrine; D005947:Glucose; D002118:Calcium; D002746:Chlorpromazine; D011700:Putrescine; D007213:Indomethacin