Age-related changes in cardiac muscarinic receptors: decreased ability of the receptor to form a high affinity agonist binding state.
Age-related changes in cardiac muscarinic receptors: decreased ability of the receptor to form a high affinity agonist binding state.
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心脏毒蕈碱受体的年龄相关变化：受体形成高亲和力激动剂结合状态的能力降低。
DOI：
10.1093/geronj/40.2.141
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Posner,P
中科院分区：
文献类型：
--
作者：
Baker,SP;Marchand,S;O'Neil,E;Nelson,CA;Posner,P
在Fischer 344大鼠3、12和24月龄时测定心室毒蕈碱胆碱能受体和激动剂的结合特性。毒蕈碱受体通过特异性(−)−[3H]苯基喹啉酸（QNB）结合确定，激动剂结合特性通过竞争试验确定。三个年龄组的受体浓度和[3H]QNB结合的解离常数均无差异。3个月和12个月大动物的心膜中，5 '；- guananyyl -imidodiphosphate （Gpp(NH)p）抑制[3H]QNB结合所需的carbachol浓度增加了16 ~ 18倍（p< 0.01） （IC50）。然而，在24个月时，Gpp（NH）仅诱导碳醇ic50值变化2.7倍（p < 0.01）。减少的位移是由于在没有Gpp（NH）的情况下测定的碳醇ic50值增加（p< 0.01）。3月龄、12月龄和24月龄动物产生乙醇IC50、shift所需的半最大Gpp(NH)p浓度无显著差异。数据表明，随着年龄的增长，毒蕈碱受体形成高亲和力激动剂结合状态的能力降低。
Cardiac ventricular muscarinic cholinergic receptors and agonist binding properties were determined in Fischer 344 rats at 3, 12, and 24 months of age. Muscarinic receptors were determined by specific (−)−[3H]quinuclidinyl benzilate (QNB) binding, and the agonist binding properties were determined by competition assays. There were no differences in the concentration of the receptor or the dissociation constant of [3H]QNB binding among the three age groups. In cardiac membranes from 3-and 12-monthold animals, 5′;-guanylyl-imidodiphosphate (Gpp(NH)p) increased by 16-to 18-fold (p< .01) the concentration of carbachol required to inhibit [3H]QNB binding by 50% (IC50). At 24 months, however, Gpp(NH)pinduced only a 2.7-fold shift in the carbachol IC50value (p < .01). The reduced shift was due to an increase in the carbachol IC50value determined in the absence of Gpp(NH)p (p< .01). There was no significant differences among the 3-, 12-, and 24-month-old animals in the half-maximal concentration of Gpp(NH)p required to produce the carbachol IC50, shift. The data indicated that with age there is a reduced ability of the muscarinic receptor to form a high affinity agonist binding state.