The present study investigated the effects of cGMP on cytosolic Ca
2+ concentration ([Ca
2+]
c) of isolated rat pancreatic β-cells. In the presence of 7.0 mM glucose, NOC 7, a nitric oxide (NO) donor, caused an increase in [Ca
2+]
c of the β-cells, which was abolished by the soluble guanylate cyclase inhibitor ODQ. Similar [Ca
2+]
c elevation was evoked by 8-bromo-cGMP. The [Ca
2+]
c elevating responses to NOC 7 and 8-bromo-cGMP were abolished by nicardipine or in a Ca
2+-free medium, but were not affected by thapsigargin, suggesting that they are produced by the Ca
2+ influx through L-type voltage-operated Ca
2+ channels. In contrast, NOC 7 and 8-bromo-cGMP decreased the [Ca
2+]
c when it was raised in advance by the elevation of external K
+ concentration to 30 mM or by 4-aminopyridine. The pretreatment with thapsigargin almost abolished the [Ca
2+]
c reduction induced by the agents, suggesting that the action is likely to be primarily attributable to an acceleration of the Ca
2+ sequestration into the endoplasmic reticulum. These results suggest that cGMP has two distinct effects on the [Ca
2+]
c of rat pancreatic β-cells: a facilitation of the Ca
2+ influx through L-type voltage-operated Ca
2+ channels and an acceleration of the Ca
2+ sequestration in the endoplasmic reticulum.
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