Muscarinic receptors in the aortae of normo- and hypertensive rats: a binding study.
The muscarinic receptors in the aorta of the normo- and hypertensive rats were characterised with tritiated acetylcholine (3H-ACh) and various muscarinic receptor antagonists. The binding of 3H-ACh to the endothelial membranes of the normotensive Wistar Kyoto rats (WKY) and the spontaneously hypertensive rats (SHR) was displaceable by nanomolar range of scopolamine but only by micromolar range of atropine and homatropine. The reverse was observed with the muscle binding sites, i.e. the 3H-ACh was displaceable by nanomolar range of atropine and homatropine but only by micromolar range of scopolamine. Pirenzepine and 4-diphenyl-acetoxy-N-methyl-piperidine metobromide (4-DAMP) displaced the binding of 3H-ACh from both tissues in the nano to micromolar range, with the displacement from the endothelial binding sites occurring at lower concentration range of the ligands. The apparent IC50 values of both compounds for the smooth muscle were 9 and 16 times greater than those for the endothelial binding sites respectively. When saturated with guanylyl-imididiphosphate (GppNHp), conversion of high to low-affinity binding site occurred in both tissues of the WKY but only in the smooth muscle of the SHR. GppNHp had no apparent effect on the binding of 3H-ACh to the endothelial binding sites confirming that the high-affinity site for 3H-ACh was missing in the endothelium of the SHR.
Sim
M K
MK
Department of Pharmacology, Faculty of Medicine, National University of Singapore.
Manjeet
S
S
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001285:Atropine / Q000378:metabolism; D001667:Binding, Competitive; D004730:Endothelium, Vascular / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010276:Parasympatholytics / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism; D010890:Pirenzepine / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012601:Scopolamine / Q000378:metabolism; D014326:Tropanes / Q000378:metabolism
D010276:Parasympatholytics; D010880:Piperidines; D011976:Receptors, Muscarinic; D014326:Tropanes; D006165:Guanylyl Imidodiphosphate; D010890:Pirenzepine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; C100236:homatropine; D012601:Scopolamine; D000109:Acetylcholine