Regulation of Glycogen Metabolism in Hepatocytes Through Adenosine Receptors. Role of Ca2+ and cAMP

Eur J Pharmacol. 2002 Feb 22;437(3):105-11. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Animals
  • Calcium / metabolism
  • Calcium / physiology
  • Cyclic AMP / metabolism
  • Cyclic AMP / physiology
  • Dose-Response Relationship, Drug
  • Egtazic Acid / analogs & derivatives*
  • Egtazic Acid / pharmacology
  • Gluconeogenesis / drug effects
  • Glycogen / metabolism*
  • Glycolysis / drug effects
  • Hepatocytes / cytology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Male
  • Phenethylamines / pharmacology
  • Purinergic P1 Receptor Agonists
  • Rats
  • Rats, Wistar
  • Receptors, Purinergic P1 / physiology*


  • Phenethylamines
  • Purinergic P1 Receptor Agonists
  • Receptors, Purinergic P1
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine
  • N(6)-cyclopentyladenosine
  • Egtazic Acid
  • Glycogen
  • Cyclic AMP
  • Adenosine
  • Calcium