Homologous sensitisation of embryonic chick atrial myocytes to adenosine: mediation by adenosine A1 receptor and guanine nucleotide binding protein.
Homologous sensitisation of embryonic chick atrial myocytes to adenosine: mediation by adenosine A1 receptor and guanine nucleotide binding protein.
复制标题
胚胎鸡心房肌细胞对腺苷的同源敏化：腺苷 A1 受体和鸟嘌呤核苷酸结合蛋白的介导。
DOI：
10.1093/cvr/27.1.102
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发表时间：
1993
影响因子：
10.8
通讯作者：
Hirsch,AJ
中科院分区：
文献类型：
--
作者：
Liang,BT;Hirsch,AJ
Objective:The aim was to characterise the process and the mechanisms of sensitisation of the atrial myocyte to adenosine receptor agonist.Methods:The ability of adenosine A1receptor to mediate inhibition of adenylyl cyclase activity and myocyte contractility was determined in atrial myocytes cultured from 14 d chick embryos. Under conditions in which the myocytes were sensitised to the effects of A1agonist, changes in the levels of adenosine A1receptor and pertussis toxin sensitive G proteins were determined and correlated with alterations in the adenylyl cyclase activity and contractile responses of the myocyte to the A1agonist.Results:Removal of adenosine from the culture medium with adenosine deaminase resulted in an enhanced ability of the adenosine A1receptor agonist R-N6-(2-phenylisopropyl)-adenosine to exert a direct, negative inotropic effect and to inhibit isoprenaline stimulated adenylyl cyclase activity. The increase in the extent of maximum inhibition of adenylyl cyclase activity and of myocyte contractility was 215(30), n=5, and 90(10)%, n=14, respectively. Binding of the antagonist radioligand [3H]-8-cyclopentyl-1,3-dipropylxanthine in membranes from myocytes pre-exposed to adenosine deaminase showed a 70% increase in the adenosine A1receptor density and a 54% increase in the proportion of the high affinity adenosine A1receptor: control 33(5)%, n=5, versus sensitised 49(3)%, n=5, p<0.01. The increase in the total number of adenosine receptors and the proportion of the high affinity form was associated with a similar increase in the level of pertussis toxin sensitive G protein(s), as determined by pertussis toxin mediated32P-ADP ribosylation and by immunoblotting. Prior exposure of the culture to the adenosine receptor antagonist 8-(p-sulphophenyl) theophylline also led to similar results.Conclusions:The data indicate that the increased level of pertussis toxin sensitive G protein(s) results in an enhanced coupling to form the high affinity adenosine A1receptor, that newly formed high affinity receptors are linked to an enhanced sensitivity of atrial myocytes to A1adenosine agonist stimulation, and that upregulation of the G protein is a mechanism mediating the homologous sensitisation of cardiac adenosine A1receptor pathway.Cardiovascular Research1993;27:102-110
