Abstract
l-Nicotine stimulates a biphasic release of [3H]dopamine from mouse striatal synaptosomes which does not persist after agonist is removed. Approximately 80% of the initial release is transient and disappears with a half-time of less than 1 min; the other 20% persists for several minutes (t 1/2, 5–10 min). Both the transient and persistent phases were investigated by 10-min exposures to agonists with an in vitro perfusion technique. A series of nicotinic agonists and antagonists were used to determine the pharmacological relationship of the two phases. Parameters measured included EC50 and V max values and desensitization rates for both phases for agonists,K i values for antagonists andK i values for low concentrations of agonists. The results are consistent with both phases being mediated by a single type of receptor. In addition, the effects of chronic nicotine treatment on transient and persistent [3H]DA release were measured. For both phases, release was decreased approximately 15% by chronic infusion of 4.0 mg/kg/hr l-nicotine. Correlation of the results with inactivation of a portion of the receptors rather than a reversible desensitization is discussed.
Footnotes
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Send reprint requests to: Allan C. Collins, IBG Campus Box 447, University of Colorado, Boulder, CO 80309.
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↵1 This work was supported by grants DA-03194 and DA-00197 from the National Institute on Drug Abuse.
- Abbreviations:
- ACh
- acetylcholine
- ATR
- atropine
- ATX
- anatoxin-a
- CARB
- carbachol
- CYT
- cytisine
- DA
- dopamine
- DEC
- decamethonium
- DFP
- diisopropyl fluorophosphate
- DHβE
- dihydro-β-erythroidine
- EPI
- (+)-epibatidine
- HEPES
- N-[2-hydroxyethyl]-piperazine-N′-[2-ethanesulfonate]
- HEX
- hexamethonium
- MEC
- mecamylamine
- MeCARB
- methylcarbachol
- MLA
- methyllycaconitine
- nAChR
- neuronal nicotinic acetylcholine receptor
- nBTX
- neuronal bungarotoxin
- NIC
- nicotine
- dTC
- d-tubocurarine
- TMA
- tetramethylammonium
- Received September 30, 1996.
- Accepted March 6, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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