Regulation of glycogen metabolism in hepatocytes through adenosine receptors. Role of Ca2+ and cAMP

• Published in: European journal of pharmacology Vol. 437; no. 3; pp. 105 - 111
• Main Authors: GONZALEZ-BENITEZ, Elizabeth, GUINZBERG, Raquel, DIAZ-CRUZ, Antonio, PINA, Enrique
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 22.02.2002
• Subjects: Adenosine - analogs & derivatives; Adenosine - pharmacology; Animals; Biological and medical sciences; Calcium - metabolism; Calcium - physiology; Cyclic AMP - metabolism; Cyclic AMP - physiology; Dose-Response Relationship, Drug; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacology; Fundamental and applied biological sciences. Psychology; Gluconeogenesis - drug effects; Glycogen - metabolism; Glycolysis - drug effects; Hepatocytes - cytology; Hepatocytes - drug effects; Hepatocytes - metabolism; Liver. Bile. Biliary tracts; Male; Phenethylamines - pharmacology; Purinergic P1 Receptor Agonists; Rats; Rats, Wistar; Receptors, Purinergic P1 - physiology; Vertebrates: digestive system; Molecular form; Calcium; Rat; Digestive system; Glycogen; Liver; Rodentia; Cyclic AMP; Metabolism; In vitro; Vertebrata; Regulation(control); Mammalia; Hepatocyte; Animal; Glycogenolysis; Intracellular; Adenosine receptor; Gluconeogenesis
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/s0014-2999(02)01299-2

The objective of this work is to identify the adenosine receptor subtype and the triggered events involved in the regulation of hepatic glycogen metabolism. Glycogenolysis, gluconeogenesis, cAMP, and cytosolic Ca2+ ([Ca2+](cyt)) were measured in isolated hepatocytes challenged with adenosine A1, A2A, and A3 receptor-selective agonists. Stimulation of adenosine receptor subtypes with selective agonists in Ca2+ media produced a dose-dependent increase in [Ca2+]cyt with A1>A2=A3, cAMP with A2A, glycogenolysis with A1>A2A>A3, and gluconeogenesis with A2A>A1>A3, in addition, a decrease in cAMP was observed with A1=A3. Comparatively, in Ca2+-free media or with a cell membrane-permeant Ca2+ chelator, activation of these adenosine receptors with the same selective agonists produced a smaller and transient rise in [Ca2+]cyt with A1=A3>A2, no rise in glycogenolysis and gluconeogenesis with A3>A1, but a full rise with A2A. Thus, in isolated rat hepatocytes activation of the adenosine A1 receptor triggered Ca2+-mediated glycogenolysis, activation of the adenosine A2A receptor stimulated cAMP-mediated gluconeogenesis, and activation of the adenosine A3 receptor increased [Ca2+]cyt and decreased cAMP with minor changes in glycogen metabolism.