title: Pharmacological and physiological properties of a putative ganglionic nicotinic receptor, alpha 3 beta 4, expressed in transfected eucaryotic cells.
abstract: Neuronal nicotinic acetylcholine receptor subunits alpha 3 (PCA48E) and beta 4S (ZPC13) were expressed in human embryonic kidney (HEK)-293 cells by calcium phosphate transfection. In the presence of atropine, acetylcholine (ACh) induced fast activating currents which exhibited desensitization and inward rectification. The EC50 for ACh was 202 +/- 32 microM with a Hill coefficient of 1.9 +/- 0.4. The rank order of nicotinic agonist potency was 1,1-dimethyl-4-phenylpiperozinium (DMPP) > cytisine = nicotine approximately equal to ACh. The maximal response elicited by DMPP was substantially less than that elicited by other agonists, suggesting that DMPP is a partial agonist. ACh (500 microM) responses were very effectively blocked by equimolar concentrations (100 microM) of the ganglionic antagonists d-tubocurarine, mecamylamine and hexamethonium. Equal concentrations of the potent muscle receptor antagonist decamethonium and the competitive antagonist dihydro-beta-erythroidine were much less effective. alpha bungaro-toxin (1 microM) had little effect on ACh-induced responses. This physiological and pharmacological profile is consistent with a ganglionic nicotinic response.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO.
authors.forename: E T
authors.initials: ET
authors.lastname: Wong
authors.forename: S G
authors.initials: SG
authors.lastname: Holstad
authors.forename: S J
authors.initials: SJ
authors.lastname: Mennerick
authors.forename: S E
authors.initials: SE
authors.lastname: Hong
authors.forename: C F
authors.initials: CF
authors.lastname: Zorumski
authors.forename: K E
authors.initials: KE
authors.lastname: Isenberg
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001392:Azocines; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011807:Quinolizines; D011978:Receptors, Nicotinic / Q000502:physiology*; D000093843:Quinolizidine Alkaloids
chemical_list: D000109:Acetylcholine; D000470:Alkaloids; D001285:Atropine; D001392:Azocines; D009538:Nicotine; D011807:Quinolizines; D011978:Receptors, Nicotinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids