Inhibition by nitric oxide of Ca2+ responses in rat pancreatic α-cells

This study examined the effect of nitric oxide (NO) on the cytosolic free Ca2+ concentration ([Ca2+](c)) of alpha-cells isolated from rat pancreatic islets. When extracellular glucose was reduced from 7 to 0 mM, about half of the alpha-cells displayed [Ca2+](c) oscillations. Nicardipine, a Ca2+ channel blocker, terminated the oscillations, while thapsigargine, an inhibitor of Ca2+-ATPase on the endoplasmic reticulum, did not affect them, suggesting that the [Ca2+](c) oscillations were produced by periodic Ca2+ influx via L-type voltage-operated Ca2+ channels. NOC 7, an NO donor, did not cause any changes in [Ca2+](c) at 7 mM glucose, but reduced [Ca2+](c) or terminated [Ca2+](c) oscillations at 0 or 2.8 mM glucose. A similar inhibitory effect on [Ca2+](c) of alpha-cells was caused by 8-bromo-cGMP. When the [Ca2+](c) of a-cells was elevated by L-arginine in the presence of N.-nitro-L-arginine, an NO synthase inhibitor, the subsequent application of NOC 7 and 8-bromo-cGMP reduced [Ca2+](c). As there is a direct relationship between [Ca2+](c) and glucagon release, these results suggest that the NO-cGMP system in rat pancreatic islets reduces glucagon release by suppressing [Ca2+](c) responses in alpha-cells. (C) 2002 Elsevier Science Inc. All rights reserved.