Regulation of ATP-sensitive K+ channels in insulinoma cells: activation by somatostatin and protein kinase C and the role of cAMP.
The actions of somatostatin and of the phorbol ester 4 beta-phorbol 12-myristate 13-acetate (PMA) were studied in rat insulinoma (RINm5F) cells by electrophysiological and 86Rb+ flux techniques. Both PMA and somatostatin hyperpolarize insulinoma cells by activating ATP-sensitive K+ channels. The presence of intracellular GTP is required for the somatostatin effects. PMA- and somatostatin-induced hyperpolarization and channel activity are inhibited by the sulfonylurea glibenclamide. Glibenclamide-sensitive 86Rb+ efflux from insulinoma cells is stimulated by somatostatin in a dose-dependent manner (half maximal effect at 0.7 nM) and abolished by pertussis toxin pretreatment. Mutual roles of a GTP-binding protein, of protein kinase C, and of cAMP in the regulation of ATP-sensitive K+ channels are discussed.
de Weille
J R
JR
Centre de Biochimie du Centre National de la Recherche Scientifique, Nice, France.
Schmid-Antomarchi
H
H
Fosset
M
M
Lazdunski
M
M
D007516:Adenoma, Islet Cell / Q000503:physiopathology*; D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D007340:Insulinoma / Q000503:physiopathology*; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D012413:Rubidium / Q000378:metabolism; D013004:Somatostatin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015221:Potassium Channels; D010566:Virulence Factors, Bordetella; D013004:Somatostatin; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D012413:Rubidium; D013755:Tetradecanoylphorbol Acetate; D005905:Glyburide