The influence of guanyl-5'-yl imidodiphosphate and sodium on muscarinic receptor binding in the rat brain and longitudinal muscle of the rat ileum.
The influence of guanyl-5'-yl imidodiphosphate and sodium on muscarinic receptor binding in the rat brain and longitudinal muscle of the rat ileum.
复制标题
鸟苷基-5-基亚胺二磷酸和钠对大鼠脑和大鼠回肠纵肌中毒蕈碱受体结合的影响。
DOI：
10.1016/0024-3205(80)90300-8
复制
发表时间：
1980
期刊：
影响因子：
6.1
通讯作者：
H. Yamamura
中科院分区：
文献类型：
--
作者：
F. Ehlert;W. Roeske;L. Rosenberger;H. Yamamura
使用特异性毒蕈碱亲和标记物[3 H]（−）二苯乙酸奎宁环酯（[3 H]（−）QNB）研究了脒基-5 ′-基亚氨基二磷酸（Gpp（NH）p）和钠对大鼠脑和大鼠回肠纵肌中毒蕈碱受体结合的影响。当通过竞争性抑制[3 H]（−）QNB与回肠纵行肌匀浆的结合进行测量时，在30 μM Gpp（NH）p存在下，氧化震颤素和卡巴胆碱的IC 50增加了3倍。相反，当在不同的大鼠脑区进行结合实验时，Gpp（NH）p仅使激动剂IC 50值略有增加。激动剂抑制曲线偏离质量作用定律，符合双结合位点模型。非线性回归分析显示，高亲和力激动剂位点在小脑（68%）、脑干（68%）、回肠纵肌（44-50%）和前脑（21-30%）中的百分比存在变异。在回肠和前脑中，Gpp（NH）p对激动剂结合的主要作用是降低高亲和力激动剂结合位点的亲和力。在小脑和脑干Gpp（NH）p没有影响。此外，Gpp（NH）p对任何组织中的拮抗剂结合没有显著影响。钠（200 mM NaCl）对毒蕈碱受体结合的影响进行了研究，前脑和回肠纵肌匀浆，并观察到钠的激动剂亲和力的优先减少。
The effects of guanyl-5′-yl imidodiphosphate (Gpp(NH)p) and sodium on muscarinic receptor binding in the rat brain and longitudinal muscle of the rat ileum were investigated using the specific muscarinic affinity label [3H](−) quinuclidinyl benzilate ([3H](−)QNB). When measured by competitive inhibition of [3H](−)QNB binding to homogenates of the longitudinal muscle of the ileum, the IC50′s of oxotremorine and carbachol increased by a factor of 3 in the presence of 30 μM Gpp(NH)p. In contrast Gpp(NH)p only produced small increases in agonist IC50values when binding experiments were done on various rat brain regions. The agonist inhibition curves deviated from the law of mass action and were consistant with a two binding site model. Nonlinear regression analysis showed variation in the percentage of high affinity agonist sites in the cerebellum (68%), brainstem (68%), longitudinal muscle of the ileum (44–50%) and forebrain (21–30%). In the ileum and forebrain, the predominant effect of Gpp(NH)p on agonist binding was a reduction in the affinity of the high affinity agonist binding site. In the cerebellum and brainstem Gpp(NH)p had no effect. Furthermore, Gpp(NH)p had no significant effect on antagonist binding in any tissue. The influence of sodium (200 mM NaCl) on muscarinic receptor binding was investigated in homogenates of the forebrain and longitudinal muscle of the ileum, and a preferential reduction of agonist affinity by sodium was observed.