Mice heterozygous for both A1 and A2A adenosine receptor genes show similarities to mice given long-term caffeine
Mice heterozygous for both A1 and A2A adenosine receptor genes show similarities to mice given long-term caffeine
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DOI：
10.1152/japplphysiol.90971.2008
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发表时间：
2009-02-01
影响因子：
3.3
通讯作者：
Fredholm, Bertil B.
中科院分区：
文献类型：
--
作者：
Yang, Jiang-Ning;Bjorklund, Olga;Fredholm, Bertil B.
杨金荣，Bjorklund O, Lindstrom-Tornqvist K, Lindgren E, Eriksson TM, Kahlstrom J, Chen JF, Schwarzschild MA, Tobler I, Fredholm BB。A(1)和A（2A）腺苷受体基因杂合的小鼠与长期摄入咖啡因的小鼠表现出相似性。中国生物医学工程学报（英文版），2009；首次发表于2008年11月26日；doi: 10.1152 / japplphysiol.90971.2008。-咖啡因被认为是通过阻断A（2A）和A(1)腺苷受体(A（2A)R和A(1)R）来发挥其兴奋作用。尽管a (2A)R的基因敲除消除了咖啡因的影响，但敲除动物的表型与咖啡因处理的动物不同。在这项研究中，我们探索了一种可能性，即通过删除a (1)R和a (2A)R基因的两个拷贝中的一个，仅仅减少a (1)R和a (2A)R的数量，就会模仿长期摄入咖啡因的某些方面。A(1)R和A(2)AR双杂合(A（1)R-A(2A)R dHz）小鼠确实具有大约一半的A(1)R和A(2A)R数量，并且A（2B）或A(3)腺苷受体(A（2B)R或A(3)R）表达几乎没有代偿性变化。稳定的腺苷类似物激活受体的能力在咖啡因和a (1)R- a (2A)R - dHz组织中向右移动。咖啡因（在饮用水中添加0.3 g/l，持续7-10天）和A(1)R-A(2A)R dHz基因型增加了运动活性（LA），降低了心率，但对体温没有显著影响。在a (1)R- a (2A)R - dHz小鼠和长期口服咖啡因的小鼠中，单次注射咖啡因的急性刺激作用减弱。因此，至少长期摄入咖啡因的某些方面可以通过基因操作来模仿A(1)R和A(2A)R。
Yang JN, Bjorklund O, Lindstrom-Tornqvist K, Lindgren E, Eriksson TM, Kahlstrom J, Chen JF, Schwarzschild MA, Tobler I, Fredholm BB. Mice heterozygous for both A(1) and A(2A) adenosine receptor genes show similarities to mice given long-term caffeine. J Appl Physiol 106: 631-639, 2009. First published November 26, 2008; doi: 10.1152/japplphysiol.90971.2008.-Caffeine is believed to exert its stimulant effects by blocking A(2A) and A(1) adenosine receptors (A(2A)R and A(1)R). Although a genetic knockout of A(2A)R eliminates effects of caffeine, the phenotype of the knockout animal does not resemble that of caffeine treatment. In this study we explored the possibility that a mere reduction of the number of A(1)Rs and A(2A)Rs, achieved by deleting one of the two copies of the A(1)R and A(2A)R genes, would mimic some aspects of long-term caffeine ingestion. The A(1)R and A(2)AR double heterozygous (A(1)R-A(2A)R dHz) mice indeed had approximately one-half the number of A(1)R and A(2A)R, and there were little compensatory changes in A(2B) or A(3) adenosine receptor (A(2B)R or A(3)R) expression. The ability of a stable adenosine analog to activate receptors was shifted to the right by caffeine and in A(1)R-A(2A)R dHz tissue. Caffeine (0.3 g/l in drinking water for 7-10 days) and A(1)R-A(2A)R dHz genotype increased locomotor activity (LA) and decreased heart rate without significantly influencing body temperature. The acute stimulatory effect of a single injection of caffeine was reduced in A(1)R-A(2A)R dHz mice and in mice treated long term with oral caffeine. Thus at least some aspects of long-term caffeine use can be mimicked by genetic manipulation of the A(1)R and A(2A)R.