Subclassification of atrial and intestinal muscarinic receptors of the rat--direct binding studies with agonists and antagonists.
1. Although extensively investigated, the extent of differences between receptors mediating negative inotropic and chronotropic responses is still unclear. In the present study atrial and intestinal muscarinic receptors were identified by [3H]-N-methyl-scopolamine ([3H]-NMS) binding and the affinities of some presumably inotropy- or chronotropy-selective agonists and several antagonists determined. 2. All the agonists tested showed similar affinity for right and left atrial receptors. Accepting an affinity difference of 0.4 log units as experimental error, none of the agonists tested was selective for either atrium. 3. Affinity differences of the cardioselective antagonists himbacine, AF-DX 116 and methoctramine and the M1-selective antagonist dicyclomine for right and left atrial muscarinic receptors were also minimal (less than 2 fold selective). When compared to intestinal receptors, AF-DX 116 was 3 to 4 fold, methoctramine 10 to 13 fold selective and himbacine and dicyclomine non-selective. 4. These data provide evidence for differences between atrial and intestinal but not between right and left atrial muscarinic receptors.
Brunner
F
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Institut für Pharmakodynamik & Toxikologie der Universität Graz, Austria.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D019832:N-Methylscopolamine; D010276:Parasympatholytics / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012602:Scopolamine Derivatives / Q000494:pharmacology
D010276:Parasympatholytics; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D000109:Acetylcholine; D019832:N-Methylscopolamine