González-Benítez Elizabeth, Guinzberg Raquel, Díaz-Cruz Antonio, Piña Enrique
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Apdo. Postal 70159, Mexico City, México, D.F., 04510, Mexico.
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+) 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.
这项工作的目的是确定腺苷受体亚型以及参与肝脏糖原代谢调节的触发事件。在用腺苷A1、A2A和A3受体选择性激动剂刺激分离的肝细胞后，测量糖原分解、糖异生、环磷酸腺苷（cAMP）和细胞溶质钙（[Ca2+]cyt）。在含Ca2+的培养基中用选择性激动剂刺激腺苷受体亚型，会使[Ca2+]cyt呈剂量依赖性增加，增加幅度为A1>A2=A3；cAMP增加，是由A2A受体介导；糖原分解增加，幅度为A1>A2A>A3；糖异生增加，幅度为A2A>A1>A3，此外，A1=A3时可观察到cAMP减少。相比之下，在无Ca2+的培养基中或使用细胞膜可渗透的Ca2+螯合剂时，用相同的选择性激动剂激活这些腺苷受体，会使[Ca2+]cyt出现较小且短暂的升高，升高幅度为A1=A3>A2，A3>A1时糖原分解和糖异生无升高，但A2A受体激活时会完全升高。因此，在分离的大鼠肝细胞中，腺苷A1受体的激活触发了Ca2+介导的糖原分解，腺苷A2A受体的激活刺激了cAMP介导的糖异生，腺苷A3受体的激活增加了[Ca2+]cyt并降低了cAMP，同时对糖原代谢有轻微影响。
