Inhibition of phosphoinositide turnover by selective muscarinic antagonists in the rat striatum. Correlation with receptor occupancy.
Inhibition of phosphoinositide turnover by selective muscarinic antagonists in the rat striatum. Correlation with receptor occupancy.
复制标题
大鼠纹状体中选择性毒蕈碱拮抗剂对磷酸肌醇周转的抑制。
DOI：
10.1016/0006-2952(88)90371-1
复制
发表时间：
1988
影响因子：
5.8
通讯作者：
Hoss,W
中科院分区：
文献类型：
--
作者：
MonsmaJr,FJ;Abood,LG;Hoss,W
In the rat corpus striatum, receptor occupancy and the inhibition of phosphoinositide turnover by muscarinic antagonists have been examined under very similar conditions with respect to tissue preparation and buffer composition. The results suggest a good correlation between receptor occupancy and inhibition by muscarinic antagonists, of the carbachol-stimulated turnover of inositol phospholipids, measured by the accumulation of [3 H] inositol phosphates in the presence of 5 mM LiCl. In the presence of 10 mM carbachol (CCh), the accumulation of labeled inositol phosphates was increased 8-fold above basal levels (ec 50= 95 μ M). Inclusion of antagonists resulted in a dose-dependent inhibition of the 0.1 mM CCh-stimulated inositol phosphate accumulation, with a rank order of potency of atropine> trihexyphenidyl> pirenzepine⪢ gallamine. Radioligand binding studies with [3 H]-l-quinucliclinyl benzilate ([3 H] QNB) in a cell aggregate preparation revealed a single class of saturable, high affinity [3 H] QNB binding sites exhibiting a K d of 74 pM and a B max, of 2.85 pmol/mg protein. The antagonists examined were able to inhibit the binding of [3 H] QNB with the same rank order of potency as for the inhibition of carbachol-stimulated phosphoinositide turnover (atropine> trihexyphenidyl> pirenzepine⪢ gallamine). Although the inhibition of phosphoinositide turnover and [3 H] QNB binding by the nonselective antagonist atropine was best described by interaction at a single site, inhibition of phosphoinositide turnover and [3 H] QNB binding by both pirenzepine, which is selective for M1 receptors, and gallamine, which is selective for M2 receptors, is complex. Pirenzepine was much more potent than gallamine for both binding to receptors and inhibiting phosphoinositide turnover. Nonlinear curve-fitting analysis indicated that slope factors for inhibition of phosphoinositide turnover (analogous to Hill coefficient for binding) by only subtype selective antagonists were significantly less than unity. The above-mentioned antagonist interactions together with the apparently multicomponent stimulation of phosphoinositide turnover by carbachol suggest that phosphoinositide turnover may be coupled to more than one muscarinic receptor subtype in the corpus striatum.
登录
查看更多内容
毒蕈碱受体数量减少，因 DFP 耐受而解离
影响因子：
3.6
作者：
T. N. Smolen;A. Smolen;A. C. Collins
通讯作者：
A. C. Collins
大鼠中[3H]哌仑西平结合的独特调节特征和区域分布为不同的 M1 和 M2 毒蕈碱受体亚型提供了证据。
影响因子：
6.1
作者：
Watson,M;Yamamura,HI;Roeske,WR
通讯作者：
Roeske,WR
大鼠脑中毒蕈碱受体偏好没食子胺的区域分布。
影响因子：
5.8
作者：
M. Price;W. Messer;W. Hoss
通讯作者：
W. Hoss
完整大鼠脑细胞中激动剂诱导的毒蕈碱乙酰胆碱受体下调。
影响因子：
5
作者：
E. El;Jong Hwa Lee
通讯作者：
Jong Hwa Lee
哌仑西平表明与脑肌醇磷脂代谢相关的毒蕈碱受体的异质性
影响因子：
4.7
作者：
S. Lazareno;D. Kendall;S. Nahorski
通讯作者：
S. Nahorski