介导豚鼠离体气管对胆碱酯类收缩反应的毒蕈碱受体的特性：去除上皮的影响

Characterization of muscarinic receptors that mediate contraction of guinea-pig isolated trachea to choline esters: effect of removing epithelium.

作者信息

Morrison K J, Vanhoutte P M

机构信息

Center for Experimental Therapeutics, Baylor College of Medicine, Houston, TX 77030.

出版信息

Br J Pharmacol. 1992 Jul;106(3):672-6. doi: 10.1111/j.1476-5381.1992.tb14393.x.

DOI:10.1111/j.1476-5381.1992.tb14393.x

PMID:1354545

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1907562/

Abstract

The muscarinic receptor subtype that mediates contraction of guinea-pig trachea, in the presence and absence of epithelium, to acetic and carbamic acid choline esters was determined by use of preferential muscarinic receptor antagonists: pirenzepine (M1 receptor), methoctramine (M2 receptor) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) (M3 receptor). 2. Acetylcholine (ACh), methacholine (MeCh), carbachol (CCh), bethanechol (BeCh) and oxotremorine induced concentration-dependent contraction of guinea-pig isolated tracheal strips in the presence and absence of epithelium. Contraction to acetic choline esters (ACh and MeCh) was augmented by removal of the epithelium, whereas contraction to carbamic acid choline esters (CCh and BeCh) and oxotremorine was not influenced by removal of the epithelium. 3. Pirenzepine, methoctramine and 4-DAMP caused parallel rightward displacements of the concentration-contraction curves to the muscarinic agonists. The pA2 values (determined from Arunlakshana-Schild graphs) for pirenzepine and 4-DAMP in guinea-pig trachea in the presence of epithelium were: ACh as the agonist, 7.6 and 9.0, respectively; CCh as the agonist, 7.6 and 9.1, respectively. The apparent pKB values for methoctramine with the same system were: ACh as the agonist, 5.6; CCh as the agonist, 5.6. Similar values were obtained with MeCh, BeCh and oxotremorine as the agonists. These values were agonist- and epithelium-independent. 4. It is concluded from the pA2 and apparent pKB values obtained for the muscarinic receptor antagonists used in this study that contraction of guinea-pig isolated trachea, with and without epithelium, to both acetic and carbamic acid choline esters is mediated via the muscarinic M3 receptor subtype.Differential contractile responses of guinea-pig trachea to acetic and carbamic acid choline esters upon the mechanical removal of the epithelium may not be explained by activation of different muscarinic receptor subtypes by these agonists.

摘要

通过使用选择性毒蕈碱受体拮抗剂：哌仑西平（M1受体）、甲溴东莨菪碱（M2受体）和4-二苯基乙酰氧基-N-甲基哌啶（4-DAMP）（M3受体），确定了在有和无上皮组织存在的情况下，介导豚鼠气管对乙酸和氨基甲酸胆碱酯收缩反应的毒蕈碱受体亚型。2. 乙酰胆碱（ACh）、醋甲胆碱（MeCh）、卡巴胆碱（CCh）、氨甲酰甲胆碱（BeCh）和氧化震颤素在有和无上皮组织存在的情况下，均可引起豚鼠离体气管条浓度依赖性收缩。去除上皮组织后，对乙酸胆碱酯（ACh和MeCh）的收缩反应增强，而对氨基甲酸胆碱酯（CCh和BeCh）和氧化震颤素的收缩反应不受上皮组织去除的影响。3. 哌仑西平、甲溴东莨菪碱和4-DAMP使毒蕈碱激动剂的浓度-收缩曲线平行右移。在有上皮组织存在的情况下，豚鼠气管中哌仑西平和4-DAMP的pA2值（根据阿隆拉克沙纳-席尔德图确定）分别为：以ACh为激动剂时，分别为7.6和9.0；以CCh为激动剂时，分别为7.6和9.1。甲溴东莨菪碱在相同系统中的表观pKB值分别为：以ACh为激动剂时，为5.6；以CCh为激动剂时，为5.6。以MeCh、BeCh和氧化震颤素为激动剂时也得到了类似的值。这些值与激动剂和上皮组织无关。4. 从本研究中使用的毒蕈碱受体拮抗剂获得的pA2和表观pKB值可以得出结论，豚鼠离体气管在有和无上皮组织时对乙酸和氨基甲酸胆碱酯的收缩是通过毒蕈碱M3受体亚型介导的。豚鼠气管在机械去除上皮组织后对乙酸和氨基甲酸胆碱酯的不同收缩反应，可能无法用这些激动剂激活不同的毒蕈碱受体亚型来解释。