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AI Sacaan, JL Dunlop and GK Lloyd
SIBIA, La Jolla, California, USA.
Neuronal acetylcholine-gated ion channel receptor-mediated [3H]- norepinephrine ([3H]-NE) and [3H]-dopamine ([3H]-DA) release from rat hippocampal and striatal slices, respectively, were compared. The nicotinic receptor agonists (-)-nicotine, (-)-cytisine and 1,1-dimethyl- 4-phenylpiperazinium iodide (DMPP) increased both [3H]-NE and [3H]-DA release in a concentration-dependent manner. The rank order of potency for the three agonists was DMPP > (-)-cytisine > (-)-nicotine for evoking [3H]-NE release and (-)-cytisine > DMPP = (-)-nicotine for releasing [3H]-DA. (-)-Cytisine acted as a partial agonist in stimulating DA release as it displayed lower efficacy and inhibited the agonistic effect of (-)-nicotine. (-)-Cytisine and (-)-nicotine were equally effective in stimulating NE release. The responses to a maximally effective concentration of (-)-nicotine, (-)-cytisine or DMPP on [3H]-NE release were blocked by 1 microM tetrodotoxin (TTX). In contrast, the effects of the various agonists on [3H]-DA release were not blocked by tetrodotoxin. The nicotinic receptor antagonists, d- tubocurarine (3-100 microM) and mecamylamine (1.0-10 microM) blocked the 3H-NE release induced by (-)-nicotine and DMPP in the rat hippocampal slice, whereas dihydro beta-erythroidine (3-300 microM) was without effect. In the striatum, mecamylamine (0.3-10 microM) and dihydro beta-erythroidine (3-100 microM) blocked the responses mediated by both agonists whereas d-tubocurarine (3-100 microM) was ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)
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