Sulfonylureas activate glycogen phosphorylase and increase cytosolic free-Ca2+ levels in isolated rat hepatocytes.
Without causing significant changes in cellular levels of cyclic adenosine monophosphate (cAMP), the addition of either glibenclamide or gliquidone to isolated rat hepatocytes caused a transient dose- and Ca(2+)-dependent activation of glycogen phosphorylase. The calculated concentrations corresponding to half-maximal activation were 5 and 2 mumol/L, respectively. In connection with this, it was observed that glibenclamide provoked a dose-dependent increase in cytosolic free-calcium concentration ([Ca2+]i) in Fura-2-loaded hepatocytes. Moreover, the presence of glibenclamide in the incubation medium accelerated the rate of Ca2+ uptake by Ca(2+)-depleted hepatocytes. These findings suggest that an increase in [Ca2+]i could mediate some of the effects of sulfonylureas in liver metabolism.
López-Alarcón
L
L
Servicio de Bioquímica Experimental, Hospital Puerta de Hierro, Universidad Autónoma de Madrid, San Martín de Porres, Spain.
Melián
E
E
Muñoz-Alonso
M J
MJ
Guijarro
C
C
Boscá
L
L
Felíu
J E
JE
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002469:Cell Separation; D003600:Cytosol / Q000378:metabolism*; D004789:Enzyme Activation; D005905:Glyburide / Q000494:pharmacology; D007477:Ions; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D006005:Phosphorylases / Q000378:metabolism*; D051381:Rats; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D007477:Ions; D013453:Sulfonylurea Compounds; C010969:gliquidone; D006005:Phosphorylases; D005905:Glyburide; D002118:Calcium