Fatty acids and cyclooxygenase and lipoxygenase pathway inhibitors modulate inositol phosphate formation in pancreatic islets.
Isolated rat pancreatic islets prelabeled with myo-[3H]inositol respond to glucose and carbamylcholine with increased [3H] inositol phosphate (InsP) production. Prostaglandin E2 (PGE2) inhibits the effects of glucose and carbamylcholine on [3H]InsP production. Ionomycin reversed the effect of PGE2 on glucose-stimulated [3H]InsP production. The cyclooxygenase inhibitors indomethacin, ibuprofen, and eicosatetraynoic acid potentiated [3H]InsP production in response to 5 and 10 mM glucose but not to 17 mM glucose. Indomethacin did not affect the carbamylcholine response. Unsaturated fatty acids, including arachidonic acid, linolenic acid, eicosapentaenoic acid, oleic acid, and eicosatetraynoic acid, increased [3H]InsP production. Arachidonic acid potentiated [3H]InsP accumulation in response to low concentrations of glucose. Indomethacin potentiated the response to arachidonic acid. delta 9-Tetrahydrocannabinol, which mobilizes endogenous fatty acids, also potentiated glucose-stimulated [3H]InsP production. The lipoxygenase inhibitors BW755C and nordihydroguaiaretic acid inhibited [3H]InsP production in response to glucose, carbamylcholine, and fatty acids. Thus, PGE2 and endogenous cyclooxygenase products antagonize InsP production in islets, whereas fatty acids promote InsP accumulation.
Laychock
S G
SG
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D007295:Inositol Phosphates; D015117:5,8,11,14-Eicosatetraynoic Acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D002217:Carbachol; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D005947:Glucose; D015232:Dinoprostone; D007052:Ibuprofen; D007213:Indomethacin