Muscarinic receptor agonist-antagonist interaction in the rat rectum: are there ways of activating the same receptors?
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.
Akah
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Oriowo
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D005703:Gallamine Triethiodide / Q000494:pharmacology; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012007:Rectum / Q000187:drug effects*
D008688:Methacholine Compounds; D010276:Parasympatholytics; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D001285:Atropine; D002217:Carbachol; D000109:Acetylcholine; D005703:Gallamine Triethiodide