参与气管降钙素基因相关肽释放的毒蕈碱受体的特性研究

Characterization of muscarinic receptors involved in tracheal CGRP release.

作者信息

Hua X Y, Back S M, Yaksh T L

机构信息

Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818.

出版信息

Neuroreport. 1994 Oct 27;5(16):2133-6. doi: 10.1097/00001756-199410270-00036.

DOI:10.1097/00001756-199410270-00036

PMID:7865762

Abstract

Application of acetylcholine (ACh) to isolated rat trachea induces an increase in calcitonin gene-related peptide (CGRP) outflow in the perfusates. The elevation of CGRP release by ACh was absent in capsaicin-desensitized preparations, suggesting that the release of peptide is derived from capsaicin-sensitive afferent nerves. ACh-induced release was not altered by hexamethonium, but was significantly attenuated by atropine, indicating involvement of the muscarinic receptor. Effects of three selective muscarinic subtype antagonists, pirenzepine (M1), methoctramine (M2) and 4-DAMP (M3) on ACh-evoked release were examined. The ordering of antagonist potency was: 4-DAMP (ED50 = 14 nM) > pirenzepine (3.8 microM) > methoctramine (> 10 microM). The results suggest that the muscarinic receptor mediating tracheal CGRP release resembles the M3 receptor subtype.

摘要

将乙酰胆碱（ACh）应用于离体大鼠气管可导致灌流液中降钙素基因相关肽（CGRP）流出增加。在辣椒素脱敏制剂中，ACh引起的CGRP释放升高不存在，这表明肽的释放源自辣椒素敏感的传入神经。六甲铵不改变ACh诱导的释放，但阿托品可显著减弱该释放，表明毒蕈碱受体参与其中。研究了三种选择性毒蕈碱亚型拮抗剂哌仑西平（M1）、甲溴东莨菪碱（M2）和4-二甲基氨基吡啶（4-DAMP，M3）对ACh诱发释放的影响。拮抗剂效力顺序为：4-DAMP（半数有效剂量[ED50]=14 nM）>哌仑西平（3.8 microM）>甲溴东莨菪碱（>10 microM）。结果表明，介导气管CGRP释放的毒蕈碱受体类似于M3受体亚型。