NITRIC-OXIDE INDUCES INTRACELLULAR CA2+ MOBILIZATION AND INCREASES SECRETION OF INCORPORATED 5-HYDROXYTRYPTAMINE IN RAT PANCREATIC BETA-CELLS

This study is the first to demonstrate that low concentrations of aqueous NO induce intracellular Ca2+ mobilization and an increase in secretory activity of rat pancreatic beta-cells. Application of NO solution (2 mu M) resulted in a transient increase in the free intracellular Ca2+ concentration ([Ca2+](i)) of isolated cells, as assessed by video ratio imaging and single wavelength microfluorimetry, Amperometry revealed a simultaneous increase in the release of preloaded 5-hydroxytryptamine from the isolated cells. The NO-induced Ca2+ response primarily involves mobilization of endoplasmic reticulum Ca2+ stores, since the response was retained when cells were transferred to low Ca2+ medium, and completely inhibited when cells were pretreated with 10 mu M thapsigargin. The Ca2+ response was also inhibited when cells were incubated with a high concentration of ryanodine (200 mu M), suggesting that Ca2+ mobilization is via a ryanodine-sensitive store.