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

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 times 10−8-1.95 times 10−6M), methacholine (8.7 times 10−8-1.1 times 10−6 M) and carbachol (1.1 times 10−7-3.5 times 10−6 M) induced contractions that were reversibly antagonized by atropine (1.9 times 10−9-4.8 times 10−8 M), 4-DAMP (1.5 times 10−8-2.86 times 10−7 M) gallamine (1.12 times 10−6-1.12 times 10−4 M) and pirenzepine (2.8 times 10−7-7.0 times 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.