U-73122 inhibits carbachol-induced increases in [Ca2+]i, IP3, and insulin release in beta-TC3 cells.
We studied the effects of the aminosteroid U-73122, a putative phospholipase C (PLC) inhibitor, on carbachol-induced increases in insulin release, [Ca2+]i, and IP3 in beta-TC3 cells. Carbachol (0.1-100 microM) increased [Ca2+]i and carbachol (0.1-1000 microM) increased insulin release dose-dependently. Carbachol (100 microM) also increased inositol 1,4,5-trisphosphate (IP3) production. U-73122 (2-12 microM) inhibited the effects of carbachol on [Ca2+]i and insulin release in a dose-dependent manner, and at the highest dose studied (12 microM) it abolished or greatly attenuated all three effects of carbachol. In contrast, U-73343 (12 microM), the analog of U-73122 that does not inhibit PLC, only inhibited the effect of carbachol on [Ca2+]i by 20%, and did not inhibit the effect of carbachol on insulin release. Since carbachol increases IP3, [Ca2+]i, and insulin release by activating PLC, these results suggested that U-73122 inhibits phospholipase C-dependent processes in beta-TC3 cells.
Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011.
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D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002217:Carbachol / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D002478:Cells, Cultured; D004347:Drug Interactions; D004963:Estrenes / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D004963:Estrenes; D007328:Insulin; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D010738:Type C Phospholipases; D002118:Calcium