title: Activation of glycogenolysis by the reduction in the extracellular calcium concentration in verapamil-perfused rat liver.
abstract: In an attempt to elucidate the role of Ca2+ flux in the initial events of hepatic glycogenolysis, extracellular Ca2+ concentration was manipulated in rat liver perfused with Ca2+ antagonistic drugs. After the liver had been perfused with a buffer containing verapamil and 1 mM CaCl2, either the addition of ethyleneglycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid to the perfusate or the replacement of the perfusate with Ca2+-free buffer caused a rapid increase in glucose output as well as 45Ca2+ efflux. Substitution of diltiazem, but not 5-20 mM LaCl2, for verapamil also stimulated glucose output and 45Ca2+ efflux. However, when Ca+-free buffer was used throughout the experiment, any modes of verapamil or diltiazem perfusion were without significant effects on glucose output or Ca2+ efflux. The increases in glucose output and 45Ca2+ efflux were not affected by either 20 microM phentolamine or 300 microM ouabain, but they were inhibited significantly by 10-100 microM trifluoperazine. These results indicate that rapid decline in the extracellular Ca2+ concentration in verapamil- or diltiazem-perfused liver initiates the change in Ca2+ equilibrium on or across plasma membrane and activates glycogenolysis through a Ca2+-dependent mechanism.
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D002132:Calcium Radioisotopes; D008112:Liver Glycogen; D011506:Proteins; D014700:Verapamil; D000242:Cyclic AMP; D006152:Cyclic GMP; D005947:Glucose; D002118:Calcium