Abstract
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)
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|