CHARACTERIZATION OF THE MUSCARINIC RECEPTOR SUBTYPE INVOLVED IN PHOSPHOINOSITIDE METABOLISM IN BOVINE TRACHEAL SMOOTH-MUSCLE
CHARACTERIZATION OF THE MUSCARINIC RECEPTOR SUBTYPE INVOLVED IN PHOSPHOINOSITIDE METABOLISM IN BOVINE TRACHEAL SMOOTH-MUSCLE
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DOI：
10.1111/j.1476-5381.1990.tb14697.x
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发表时间：
1990-02-01
影响因子：
7.3
通讯作者：
ZAAGSMA, J
中科院分区：
文献类型：
--
作者：
ROFFEL, AF;MEURS, H;ZAAGSMA, J
在经典的Schild分析中，除了M1选择性拮抗剂哌仑西平外，还使用M2选择性拮抗剂AF-DX 116和M3选择性拮抗剂4-二苯基乙酰氧基-N-甲基哌啶（4-DAMP）甲溴化物鉴定了参与乙酰胆碱诱导的牛气管平滑肌磷酸肌醇代谢增强的毒蕈碱受体亚型。所有的拮抗剂移动乙酰甲胆碱剂量-反应曲线向右平行和浓度依赖性的方式，产生Schild图与斜率没有显着不同的单位。pA 2值（哌仑西平、AF-DX 116和4-DAMP甲溴化铵分别为6.94、6.32和8.54）表明，根据我们以前的收缩研究，该组织中存在的M3（平滑肌/腺体）而不是M2（心脏）毒蕈碱受体亚型介导磷酸肌醇转换。结果提供了额外的证据参与磷酸肌醇营业额之间的药物力学耦合毒蕈碱受体刺激和收缩（牛气管）平滑肌。
The muscarinic receptor subtype involved in the methacholine-induced enhancement of phosphoinositide metabolism in bovine tracheal smooth muscle was identified by using the M2 selective antagonist AF-DX 116 and the M3-selective antagonist 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) methobromide, in addition to the M1-selective antagonist pirenzepine, in a classical Schild analysis. All the antagonists shifted the methacholine dose-response curve to the right in a parallel and concentration-dependent fashion, yielding Schild plots with slopes not significantly different from unity. The pA2 values (6.94, 6.32 and 8.54 for pirenzepine, AF-DX 116 and 4-DAMP methobromide resepectively) indicate that it is the M3 (smooth muscle/glandular), but not the M2 (cardiac) muscarinic receptor subtype, present in this tissue, that mediates phosphoinositide turnover, in accordance with our previous contractile studies. The results provide additional evidence for the involvement of phosphoinositide turnover in the pharmacomechanical coupling between muscarinic receptor stimulation and contraction in (bovine tracheal) smooth muscle.