PMID: 7932202Sep 1, 1994Paper

Arginine vasopressin-stimulated insulin secretion and elevation of intracellular Ca++ concentration in rat insulinoma cells: influences of a phospholipase C inhibitor 1-[6-[[17 beta-methoxyestra-1,3,5(10)-trien- 17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122) and a phospholipase A2 inhibitor N-(p-amylcinnamoyl)anthranilic acid

The Journal of Pharmacology and Experimental Therapeutics
T H ChenW H Hsu

Abstract

The present study investigated the mechanism by which arginine vasopressin (AVP) increases insulin secretion in rat insulinoma (RINm5F) cells by using a specific phospholipase C (PLC) inhibitor, 1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17- yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122), and a phospholipase A2 (PLA2) inhibitor, N-(p-amylcinnamoyl)anthranilic acid (ACA). AVP (0.1-100 nM) increased insulin secretion and cytosolic free Ca++ concentration ([Ca++]i) dose-dependently. AVP-induced increases in the intracellular concentration of inositol 1,4,5-trisphosphate (IP3) and [Ca++]i were dose-dependently inhibited by U-73122 (2-8 microM). At 8 microM, U-73122 abolished AVP's effect on IP3 and [Ca++]i, but AVP-induced increases in insulin secretion were only reduced by 35%. In contrast, 8 microM U-73122 did not reduce the ionomycin (a Ca++ ionophore, 100 nM)-induced increase in [Ca++]i. The discrepancy between the results of [Ca++]i and insulin secretion in U-73122 experiments is indicative of the multiple signal transduction pathways associated with the activation of AVP receptors, specifically the Ca(++)-independent pathway. The phospholipase A2 inhibitor ACA (100 microM) did not antagonize AVP (10 nM)-induced increases i...Continue Reading

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