title: Pharmacological characteristics of the endothelial target for acetylcholine induced vascular relaxation.
abstract: The pharmacological characteristics of the endothelial target for acetylcholine induced vascular relaxation were investigated in this experiment. The isolated preparations of arteries were suspended for the measurement of isometric force in modified Krebs-Ringer bicarbonate solution (37 degrees C aerated with 95% O2 and 5% CO2). Similar to acetylcholine, carbachol rather than thiocholine, butylcholine and choline could induce endothelium-dependent relaxation. Among cholinergic receptor agonists, arecoline and oxotremorine rather than nicotine could mimic the effects of acetylcholine. But muscarinic agonist pilocarpine had no effect. This phenomenon was observed in rat, cat and rabbit aorta, as well as cat mesenteric. femoral and renal arteries. The new compound tricyclopinate and phenyl cyclopentyl hydroxyl-ethoxy quinuclidines, the competitive antagonists against muscarinic receptors, displayed noncompetitive antagonism against the endothelial target for acetylcholine. Among the six isomers of the novel compound 2-(2'-cyclopentyl-2'-phenyl-2'-hydroxyl-ethoxy) tropane, the isomers with IS-2alpha-2'R and 1S-2alpha-2'S configuration caused the dose-response curves of acetylcholine for inducing vascular relaxation shift rightward with a parallel manner, while the isomers IR-2alpha-2'R and IR-2alpha-2'S with a nonparallel manner. In addition, the antagonistic effects of the isomer IS-2alpha-2'R against the endothelial target for acetylcholine and against muscarinic receptors were 4570 and 10 times greater than those of the isomer IS-2alpha-2'S respectively. In conclusion, the endothelial target for acetylcholine had the unique pharmacological characteristics different from those of muscarinic receptors.
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Shan
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
mesh_terms: D000109:Acetylcholine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002415:Cats; D018678:Cholinergic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D013045:Species Specificity
chemical_list: D018678:Cholinergic Agents; D011976:Receptors, Muscarinic; D002217:Carbachol; D000109:Acetylcholine; D009638:Norepinephrine