title: Characterization of nicotinic acetylcholine receptor-mediated [(3)H]-dopamine release from rat cortex and striatum.
abstract: The objective of this study was to use a new high throughput method to compare nicotinic acetylcholine receptor (nAChR)-mediated [(3)H]-dopamine (DA) release from slices of rat striatum and cortex. (-)Nicotine, (-)-cytisine, 1,1-dimethyl-4-phenyl-piperazinium (DMPP), and (+/-)-epibatidine evoked release of striatal [(3)H]-DA with pEC(50) values of 6.7, 8.25, 5.11, and 9.08, respectively. The same agonists evoked release of cortical [(3)H]-DA with pEC(50) values of 6.98, 8.06, 5.58, and 9.59. Relative to (-)-nicotine, (-)-cytisine was a partial agonist in both tissues. In contrast, the maximal response evoked by DMPP differed between the two tissues. The rank order of potency for antagonists to block DA release was the same (mecamylamine (Mec)>dihydro-beta-erythroidine (DHbetaE)>hexamethonium (Hex)>D-tubocurarine (D-TC)); however, the pIC(50) values varied between the two regions. Whereas Mec potently antagonized (-)-nicotine-evoked DA release similarly from striatum and cortex, with pIC(50) values of 6.07 and 6.53 respectively, the values obtained for DHbetaE, D-TC and Hex differed. Additionally, the present study was able to distinguish exocytotic vesicular-mediated from transporter-mediated DA release, by altering temperature of the incubation and exclusion of calcium. Assays carried out under these conditions indicate that approximately 60% of nicotine-evoked cortical DA release was likely mediated through the DA transporter. In contrast, under the same conditions only 15%-20% of striatal release appeared to be transporter-mediated. We conclude that the relative contributions of the mechanisms by which (-)-nicotine evokes DA release differ between striatum and cortex. In addition, the data suggest that the subtypes of nAChRs involved in regulating [(3)H]-DA release may be somewhat different in the two tissues.
authors.affiliation: Neurological and Urological Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6125, USA. pamela.puttfarcken@abbott.com
authors.forename: P S
authors.initials: PS
authors.lastname: Puttfarcken
authors.forename: I
authors.initials: I
authors.lastname: Jacobs
authors.forename: C R
authors.initials: CR
authors.lastname: Faltynek
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001392:Azocines; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011807:Quinolizines; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013696:Temperature; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D001392:Azocines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004246:Dimethylphenylpiperazinium Iodide; D004298:Dopamine; D009538:Nicotine; D018722:Nicotinic Agonists; D011725:Pyridines; D011807:Quinolizines; D011978:Receptors, Nicotinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids; C082748:epibatidine