PHARMACOLOGICAL AND PHYSIOLOGICAL-PROPERTIES OF A PUTATIVE GANGLIONICNICOTINIC RECEPTOR, ALPHA(3)BETA(4), EXPRESSED IN TRANSFECTED EUKARYOTIC CELLS

Neuronal nicotinic acetylcholine receptor subunits alpha(3) (PCA48E) a nd beta(4)S (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 EC(50) for ACh was 202 /- 32 mu M with a Hill coefficient of 1.9 +/- 0.4. The rank order of n icotinic agonist potency was 1,1-dimethyl-4-phenylpiperozinium (DMPP) > cytisine = nicotine congruent to ACh. The maximal response elicited by DMPP was substantially less than that elicited by other agonists, s uggesting that DMPP is a partial agonist. ACh (500 mu M) responses wer e very effectively blocked by equimolar concentrations (100 mu M) of t he ganglionic antagonists d-tubocurarine, mecamylamine and hexamethoni um. Equal concentrations of the potent muscle receptor antagonist deca methonium and the competitive antagonist dihydro-beta-erythroidine wer e much less effective. alpha bungarotoxin (1 mu M) had little effect o n ACh-induced responses. This physiological and pharmacological profil e is consistent with a ganglionic nicotinic response.