Pharmacological and physiological properties of a putative ganglionic nicotinic receptor, alpha 3 beta 4, expressed in transfected eucaryotic cells.
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.
Wong
E T
ET
Department of Neurology, Washington University School of Medicine, St. Louis, MO.
Holstad
S G
SG
Mennerick
S J
SJ
Hong
S E
SE
Zorumski
C F
CF
Isenberg
K E
KE
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
D000109:Acetylcholine; D000470:Alkaloids; D001285:Atropine; D001392:Azocines; D009538:Nicotine; D011807:Quinolizines; D011978:Receptors, Nicotinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids