Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait.
Med Princ Pract. 2011;20(6):530-7. doi: 10.1159/000328419. Epub 2011 Oct 4.
Carbachol-induced contraction of the rat colon is impaired in rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. The main objective of this study was to examine the effect of colitis on the expression and function of muscarinic (M) receptor subtypes in the rat colon.
Rats (n = 80) were treated with TNBS and used 5 days later for measurement of contractility, myeloperoxidase activity, histology and expression of muscarinic receptor isoforms using Western blot analysis.
Carbachol produced concentration-dependent contractions of colonic segments from control (n = 40) and TNBS-treated (n = 40) rats with no significant difference in potency. However, the maximum response to carbachol was significantly reduced in colon segments of TNBS-treated rats. The selective muscarinic receptor antagonists 4-diphenylacetoxy-N-methyl piperidine (4-DAMP, M(3)), pirenzepine (M(1)) and methoctramine (M(2)) antagonized carbachol-induced contraction in control (9.1 ± 0.1, 6.7 ± 0.3 and 6.0 ± 0.1, respectively) and TNBS-treated rats (9.2 ± 0.2, 6.9 ± 0.2, 6.7 ± 0.2). The -logK(B) values in control rats are consistent with an action of carbachol on muscarinic M(3) receptors. There was no significant difference in -logK(B) values for 4-DAMP and pirenzepine in control and TNBS-treated rats, but methoctramine was fivefold more potent in TNBS-treated rats, possibly indicating an increased contribution of muscarinic M(2) receptors to carbachol-induced contraction in the inflamed colon. The expression of M(2) receptors was also significantly increased in colon segments from TNBS-treated rats, confirming the increased role of muscarinic M(2) receptors in the inflamed colon.
The data show that while only M(3) receptors appeared to mediate carbachol-induced contraction in control segments, expression of both M(2) and M(3) receptors was increased in the inflamed rat colon.
三硝基苯磺酸（TNBS）诱导的结肠炎会使大鼠的结肠对卡巴胆碱诱导的收缩作用受损。本研究的主要目的是研究结肠炎对大鼠结肠中毒蕈碱（M）受体亚型的表达和功能的影响。
用 TNBS 处理大鼠（n = 80），5 天后用于测量收缩性、髓过氧化物酶活性、组织学和使用 Western blot 分析检测毒蕈碱受体亚型的表达。
卡巴胆碱引起对照（n = 40）和 TNBS 处理（n = 40）大鼠结肠段的浓度依赖性收缩，其效力无显著差异。然而，在 TNBS 处理的大鼠结肠段，对卡巴胆碱的最大反应明显降低。选择性毒蕈碱受体拮抗剂 4-二苯乙氧基-N-甲基哌啶（4-DAMP，M（3））、哌仑西平（M（1））和甲硫氧嘧啶（M（2））拮抗对照（9.1 ± 0.1、6.7 ± 0.3 和 6.0 ± 0.1）和 TNBS 处理大鼠（9.2 ± 0.2、6.9 ± 0.2、6.7 ± 0.2）中卡巴胆碱诱导的收缩。对照大鼠的-logK(B)值与卡巴胆碱对毒蕈碱 M(3)受体的作用一致。对照和 TNBS 处理大鼠中 4-DAMP 和哌仑西平的-logK(B)值无显著差异，但甲硫氧嘧啶在 TNBS 处理大鼠中的效力增加了五倍，可能表明在炎症结肠中，毒蕈碱 M(2)受体对卡巴胆碱诱导的收缩作用增加。M(2)受体的表达在 TNBS 处理的大鼠结肠段也显著增加，证实了毒蕈碱 M(2)受体在炎症结肠中的作用增加。
数据表明，虽然仅 M(3)受体似乎介导对照段中卡巴胆碱诱导的收缩，但在炎症大鼠结肠中 M(2)和 M(3)受体的表达均增加。
