Atropine- and scopolamine-resistant subtypes of muscarinic receptors in the rabbit aorta.
Tritiated acetylcholine ([3H]ACh) binds specifically to different muscarinic binding sites in the rabbit aorta. The binding of [3H]ACh to endothelial membranes was displacable by nanomolar concentrations of scopolamine but only by micromolar concentrations of atropine and homatropine. The reverse was true for smooth muscle membranes, i.e. [3H]ACh binding was displacable by nanomolar concentrations of atropine and homatropine but only by micromolar concentrations of scopolamine. Pirenzepine, AF-DX 116 and 4-diphenyl-acetoxy-N-methylpiperidine methobromide (4-DAMP) displaced the binding of [3H]ACh from both tissues in the nano- to micromolar range. Our findings indicate that endothelial receptors are characterised by a high affinity for scopolamine, which possesses a scopine base, and that muscle binding sites have a high affinity for antagonists possessing a tropine base (atropine, homatropine). Both the endothelial and smooth muscle binding sites have a low affinity for AF-DX 116, indicating that they are not of the cardiac type.
Manjeet
S
S
Department of Pharmacology, Faculty of Medicine, National University of Singapore.
Sim
M K
MK
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001285:Atropine / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012601:Scopolamine / Q000494:pharmacology*
D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D009569:Nitric Oxide; D006165:Guanylyl Imidodiphosphate; D001285:Atropine; D012601:Scopolamine