STIMULATION OF GLYCOGENOLYSIS AND VASOCONSTRICTION BY ADENOSINE AND ADENOSINE-ANALOGS IN THE PERFUSED-RAT-LIVER
STIMULATION OF GLYCOGENOLYSIS AND VASOCONSTRICTION BY ADENOSINE AND ADENOSINE-ANALOGS IN THE PERFUSED-RAT-LIVER
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DOI：
10.1042/bj2480035
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发表时间：
1987-11-15
影响因子：
4.1
通讯作者：
OLSON, MS
中科院分区：
文献类型：
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作者：
BUXTON, DB;FISHER, RA;OLSON, MS
向灌流的大鼠肝脏中注入腺苷可导致葡萄糖输出量、门静脉压力、流出液[乳酸]/[丙酮酸]比值和O2消耗的一过性增加。8-苯茶碱(10微米)抑制腺苷的反应，而双嘧达莫(50微米)则增强腺苷的血管收缩作用。腺苷类似物的效价顺序为：5‘’-N-乙基氨基腺苷(NECA)>；L-苯基异丙基腺苷；环己基腺苷>；D-苯基异丙基腺苷；2-氯腺苷；腺苷；腺苷作用与A2亚型的P1-嘌呤受体调节的腺苷作用一致。肝脏对重复注射腺苷的反应表现出相应的脱敏反应。在较低的灌流液钙离子浓度下，腺苷对肝脏的影响减弱。消炎痛可降低肝脏对腺苷和NECA的反应。腺苷可刺激离体肝细胞糖原磷酸化酶的活性，而NECA对肝细胞无影响。双嘧达莫(50微米)可抑制肝细胞对腺苷的反应，但8-苯基茶碱(10微米)对腺苷的反应不受抑制。目前的研究表明，虽然腺苷对实质细胞有直接作用，但腺苷通过A2-嘌呤能受体对另一种肝细胞的间接作用似乎在灌流的肝脏中起作用。
Infusion of adenosine into perfused rat livers resulted in transient increases in glucose output, portal-vein pressure, the effluent perfusate [lactate]/[pyruvate] ratio, and O2 consumption. 8-Phenyltheophylline (10 .mu.M) inhibited adenosine responses, whereas dipyhridamole (50 .mu.M) potentiated the vasoconstrictive effect of adenosine. The order of potency for adenosine analogues was: 5''-N-ethylcarboxamidoadenosine (NECA) > L-phenylisopropyladenosine > cyclohexyladenosine > D-phenylisopropyladenosine > 2-chloroadenosine > adenosine, consistent with adenosine actions modulated through P1-purine receptors of the A2-subtype. Hepatic responses exhibited homologous desensitization in response to repeated infusion of adenosine. Adenosine effects on the liver were attenuated at lower perfusate Ca2+ concentrations. Indomethacin decreased hepatic responses to both adenosine and NECA. Whereas adenosine stimulated glycogen phosphorylase activity in isolated hepatocytes, NECA caused no effect in hepatocytes. The response to adenosine in hepatocytes was inhibited by dipyridamole (50 .mu.M), but not 8-phenyltheophylline (10 .mu.M). The present study indicates that, although adenosine has direct effects on parenchymal cells, indirect effects of adenosine, mediated through the A2-purinergic receptors on another hepatic cell type, appear to play a role in the perfused liver.