Pharmacological characterization of neuronal acetylcholine gated ion channel receptor-mediated hippocampal norepinephrine and striatal dopamine release from rat brain slices.
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)
Sacaan
A I
AI
SIBIA, La Jolla, California, USA.
Dunlop
J L
JL
Lloyd
G K
GK
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*
D007473:Ion Channels; D011978:Receptors, Nicotinic; D004298:Dopamine; D009638:Norepinephrine