Somatostatin induces hyperpolarization in pancreatic islet alpha cells by activating a G protein-gated K+ channel.
Somatostatin inhibits glucagon-secretion from pancreatic alpha cells but its underlying mechanism is unknown. In mouse alpha cells, we found that somatostatin induced prominent hyperpolarization by activating a K+ channel, which was unaffected by tolbutamide but prevented by pre-treating the cells with pertussis toxin. The K+ channel was activated by intracellular GTP (with somatostatin), GTPgammaS or Gbetagamma subunits. It was thus identified as a G protein-gated K+ (K(G)) channel. RT-PCR and immunohistochemical analyses suggested the K(G) channel to be composed of Kir3.2c and Kir3.4. This study identified a novel ionic mechanism involved in somatostatin-inhibition of glucagon-secretion from pancreatic alpha cells.
Department of Pharmacology II, Faculty of Medicine and Graduate School of Medicine, Osaka University, Suita, Japan.
Y
Y
Yoshimoto
Y
Y
Fukuyama
Y
Y
Horio
A
A
Inanobe
M
M
Gotoh
Y
Y
Kurachi
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007150:Immunohistochemistry; D015640:Ion Channel Gating / Q000502:physiology*; D007515:Islets of Langerhans / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger / Q000378:metabolism; D013004:Somatostatin / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D010566:Virulence Factors, Bordetella; D013004:Somatostatin; D006160:Guanosine Triphosphate; D005934:Glucagon; D014044:Tolbutamide; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000109:Acetylcholine