Regulation of glycogen metabolism in hepatocytes through adenosine receptors. Role of Ca2+ and cAMP.
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.
González-Benítez
Elizabeth
E
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Apdo. Postal 70159, Mexico City, México, D.F., 04510, Mexico.
Guinzberg
Raquel
R
Díaz-Cruz
Antonio
A
Piña
Enrique
E
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects; D006003:Glycogen / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology*
D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; C048599:N(6)-cyclopentyladenosine; D004533:Egtazic Acid; D006003:Glycogen; D000242:Cyclic AMP; D000241:Adenosine; D002118:Calcium