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Blockade of nicotinic receptor‐mediated release of dopamine from striatal synaptosomes by chlorisondamine and other nicotinic antagonists administered in vitro

Blockade of nicotinic receptor‐mediated release of dopamine from striatal synaptosomes by... 1 Central nicotinic receptor function examined in vitro, by measuring nicotine‐induced (3H)‐dopamine release from rat striatal synaptosomes. 2 The agonists (–)‐nicotine, acetylcholine, 1,1‐dimethyl‐4‐phenylpiperazinium (DMPP) and cytisine (10−7–10−4 m) all increased (3H)‐dopamine release in a concentration‐dependent manner. Cytisine did not produce a full agonist response, compared to the other agonists. 3 The actions of nicotine, acetylcholine and cytisine were largely dependent on external Ca2+. In contrast, DMPP (10−5 and 10−4 m) evoked a marked release of (3H)‐dopamine even in the absence of Ca2+. Nevertheless, in the presence of external Ca2+, responses to DMPP were completely blocked by the nicotinic antagonists chlorisondamine and mecamylamine (5 × 10−5 m); in the absence of external Ca2+, blockade was only partial. 4 Chlorisondamine, mecamylamine and dihydro‐β‐erythroidine (10−8–10−4 m) produced a concentration‐dependent block of responses to nicotine (10−6 m). Approximate IC50 values were 1.6, 0.3 and 0.2 × 10−6, respectively. Chlorisondamine and mecamylamine blocked responses to nicotine (10−7–10−4 m) insurmountably, whereas dihydro‐β‐erythroidine behaved in a surmountable fashion. 5 The occurrence of use‐dependent block was tested by briefly pre‐exposing the synaptosomes to nicotine during superfusion with antagonist, and determining the response to a subsequent nicotine application. Consistent with a possible channel blocking action, brief pre‐exposure to agonist increased the antagonist potency of chlorisondamine (approximately 25 fold). No significant use‐dependent block was detected with dihydro‐β‐erythroidine. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Blockade of nicotinic receptor‐mediated release of dopamine from striatal synaptosomes by chlorisondamine and other nicotinic antagonists administered in vitro

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References (57)

Publisher
Wiley
Copyright
1994 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1111/j.1476-5381.1994.tb14749.x
Publisher site
See Article on Publisher Site

Abstract

1 Central nicotinic receptor function examined in vitro, by measuring nicotine‐induced (3H)‐dopamine release from rat striatal synaptosomes. 2 The agonists (–)‐nicotine, acetylcholine, 1,1‐dimethyl‐4‐phenylpiperazinium (DMPP) and cytisine (10−7–10−4 m) all increased (3H)‐dopamine release in a concentration‐dependent manner. Cytisine did not produce a full agonist response, compared to the other agonists. 3 The actions of nicotine, acetylcholine and cytisine were largely dependent on external Ca2+. In contrast, DMPP (10−5 and 10−4 m) evoked a marked release of (3H)‐dopamine even in the absence of Ca2+. Nevertheless, in the presence of external Ca2+, responses to DMPP were completely blocked by the nicotinic antagonists chlorisondamine and mecamylamine (5 × 10−5 m); in the absence of external Ca2+, blockade was only partial. 4 Chlorisondamine, mecamylamine and dihydro‐β‐erythroidine (10−8–10−4 m) produced a concentration‐dependent block of responses to nicotine (10−6 m). Approximate IC50 values were 1.6, 0.3 and 0.2 × 10−6, respectively. Chlorisondamine and mecamylamine blocked responses to nicotine (10−7–10−4 m) insurmountably, whereas dihydro‐β‐erythroidine behaved in a surmountable fashion. 5 The occurrence of use‐dependent block was tested by briefly pre‐exposing the synaptosomes to nicotine during superfusion with antagonist, and determining the response to a subsequent nicotine application. Consistent with a possible channel blocking action, brief pre‐exposure to agonist increased the antagonist potency of chlorisondamine (approximately 25 fold). No significant use‐dependent block was detected with dihydro‐β‐erythroidine.

Journal

British Journal of Pharmacology – Wiley

Published: Feb 1, 1994

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