目的探讨毒蕈碱受体亚型对人食管下括约肌套索纤维和钩状纤维胆碱能收缩的调节作用。方法选取高位食管中段癌行食管大部切除术患者32例,取食管、胃接合部标本分离套索纤维和钩状纤维,做M1~M4受体选择性拮抗剂哌仑西平、美索曲明、4-DAMP、托品酰胺的Schild曲线,并由此计算pA2。结果①M1~M4受体选择性拮抗剂均使ACh诱导套索纤维和钩状纤维的浓度—效应曲线发生右移,每条拮抗曲线形状类似。②4-DAMP在两肌纤维的pA2分别是8.18±0.76和8.05±1. 11,较其它3种拮抗剂大(F=47,4,P=0.00),而同一拮抗剂在两肌纤维的pA2无差异(F=1.36,P=0.24)。结论ACh诱导两种肌纤维的收缩主要由M3受体介导;2种肌纤维间没有毒蕈碱受体亚型功能的差异。
Aim To explore the regulation of muscarinic receptor subtypes on cholinergic contraction of the sling and clasp fibers of human lower esophageal sphincter in vitro. Methods Smooth muscles strips of the sling and clasp fibers were obtained from 32 patients who underwent subtotal esophagectomy for middle thoracic esophageal carcinoma. Schild plots of M1-M4 receptors selective antagonist, pirenzepine, methoctramine, 4-DAMP and tropicamide were generated to determine their pA2, respectively. Results ① Every antagonists to Ml-M4 receptors produced parallel right-ward shifts in the concentration-response curves induced by ACh in the sling and clasp fibers. All curves were not significantly different from unity. ②The pA2 of 4-DAMP in both fibers were 8.18 ± 0. 76 and 8.05 ± 1.11, respectively, and much greater than other three antagonists ( F = 47.4, P = 0. 00). However, there was no significant difference in the pA2 of every antagonist in the sling and clasp fibers ( F = 1.36, P = 0. 24). Conclusions ACh induces contraction of the sling and clasp fibers mainly via the M3 receptor. There is no difference in function of muscarinic receptor subtypes between both muscle fibers.