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 microM) 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 microM thapsigargin. The Ca2+ response was also inhibited when cells were incubated with a high concentration of ryanodine (200 microM), suggesting that Ca2+ mobilization is via a ryanodine-sensitive store.
Willmott
N J
NJ
University Department of Pharmacology, Oxford, UK.
Galione
A
A
Smith
P A
PA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D013729:Terpenes; D012433:Ryanodine; D009569:Nitric Oxide; D012701:Serotonin; D004533:Egtazic Acid; D019284:Thapsigargin; D002118:Calcium