大鼠直肠中毒蕈碱受体激动剂与拮抗剂的相互作用：是否存在激活相同受体的方法？

Muscarinic receptor agonist-antagonist interaction in the rat rectum: are there ways of activating the same receptors?

作者信息

Akah P A, Oriowo M A

出版信息

J Pharm Pharmacol. 1985 Aug;37(8):589-92. doi: 10.1111/j.2042-7158.1985.tb03078.x.

DOI:10.1111/j.2042-7158.1985.tb03078.x

Abstract

The interaction between the muscarinic receptor agonists, carbachol, acetylcholine (ACh) and methacholine, and antagonists, atropine, gallamine, 4-DAMP and pirenzepine, was studied on the rat isolated rectum preparation. ACh (1.93 X 10(-8)-1.95 X 10(-6) M), methacholine (8.7 X 10(-8)-1.1 X 10(-6) M) and carbachol (1.1 X 10(-7)-3.5 X 10(-6) M) induced contractions that were reversibly antagonized by atropine (1.9 X 10(-9)-4.8 X 10(-8) M), 4-DAMP (1.5 X 10(-8)-2.86 X 10(-7) M) gallamine (1.12 X 10(-6)-1.12 X 10(-4) M) and pirenzepine (2.8 X 10(-7)-7.0 X 10(-6) M). The pA2 values were atropine: 8.99 +/- 0.28, 9.29 +/- 0.14 and 8.86 +/- 0.05; 4-DAMP: 8.39 +/- 0.10, 8.66 +/- 0.15 and 8.26 +/- 0.30, gallamine: 5.85 +/- 0.23, 5.73 +/- 0.25 and 5.96 +/- 0.10 and pirenzepine: 6.85 +/- 0.44, 7.17 +/- 0.13 and 7.21 +/- 0.03 against ACh, methacholine and carbachol, respectively. The experimental dose-ratio (atropine + gallamine) was greater than the expected dose-ratio (as predicted by the Paton & Rang rule) for ACh and methacholine while the experimental dose-ratio closely approximates the expected dose-ratio for carbachol. It is suggested that atropine, 4-DAMP pirenzepine and gallamine act on the same receptors but gallamine allosterically altered the binding of the agonists and antagonists to varying extents.

摘要

在大鼠离体直肠标本上研究了毒蕈碱受体激动剂卡巴胆碱、乙酰胆碱（ACh）和醋甲胆碱与拮抗剂阿托品、加拉明、4-二甲基氨基吡啶（4-DAMP）和哌仑西平之间的相互作用。ACh（1.93×10⁻⁸ - 1.95×10⁻⁶ M）、醋甲胆碱（8.7×10⁻⁸ - 1.1×10⁻⁶ M）和卡巴胆碱（1.1×10⁻⁷ - 3.5×10⁻⁶ M）引起的收缩可被阿托品（1.9×10⁻⁹ - 4.8×1₀⁻⁸ M）、4-DAMP（1.5×10⁻⁸ - 2.86×10⁻⁷ M）、加拉明（1.12×10⁻⁶ - 1.12×10⁻⁴ M）和哌仑西平（2.8×10⁻⁷ - 7.0×10⁻⁶ M）可逆性拮抗。针对ACh、醋甲胆碱和卡巴胆碱，pA₂值分别为：阿托品：8.99±0.28、9.29±0.14和8.86±0.05；4-DAMP：8.39±0.10、8.66±0.15和8.26±0.30；加拉明：5.85±ⱨ.23、5.73±0.25和5.96±0.10；哌仑西平：6.85±0.44、7.17±0.13和7.21±0.03。对于ACh和醋甲胆碱，实验剂量比（阿托品 + 加拉明）大于预期剂量比（如根据帕顿和兰格规则预测），而对于卡巴胆碱，实验剂量比与预期剂量比密切接近。提示阿托品、4-DAMP、哌仑西平和加拉明作用于相同受体，但加拉明在不同程度上变构改变了激动剂和拮抗剂的结合。