Protein kinase C regulation of dopamine transporter initiated by nicotinic receptor activation in slices of rat prefrontal cortex.
We previously reported that activation of nicotinic receptors causes an enhancement in amphetamine-stimulated release of dopamine via its transporter from slices of prefrontal cortex, but no such enhancement of release from slices of nucleus accumbens or striatum. The nicotinic receptors mediating the enhancement most likely contain alpha4 and beta2 subunits based upon pharmacological characterization. In this study, we sought to characterize the second messenger systems associated with the nicotine-mediated response. Sodium channel involvement was confirmed by the observation that tetrodotoxin blocked nicotine-mediated enhancement, whereas veratridine or elevated K(+) mimicked the enhancement seen with nicotine. Inclusion of EGTA blocked nicotine-mediated enhancement, suggesting that, even though no exogenous Ca(2+) was added, endogenous stores were required for the enhancement. The enhancement by nicotine was also abolished by the L-type voltage-dependent calcium channel (VDCC) antagonist nitrendipine, but not by the N-type VDCC antagonist omega-conotoxin GVIA. Finally, inhibition of protein kinase C also abolished the nicotine-mediated enhancement of amphetamine-stimulated dopamine release, whereas inhibitors of Ca(2+)/calmodulin kinase II did not. These findings establish that nicotine can exert selective effects on dopamine transporter activity in prefrontal cortex, an area involved in cognition and learning.
Drew
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AE
Department of Pharmacology, The George Washington University Medical Center, Washington DC 20037, USA.
Werling
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LL
D000470:Alkaloids; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009538:Nicotine / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems; D015222:Sodium Channels / Q000502:physiology; D019311:Staurosporine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium; D014701:Veratridine / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D000470:Alkaloids; D053119:Benzophenanthridines; D002121:Calcium Channel Blockers; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010617:Phenanthridines; D011978:Receptors, Nicotinic; D015222:Sodium Channels; D014316:Tritium; D013779:Tetrodotoxin; D004533:Egtazic Acid; D009538:Nicotine; D014701:Veratridine; D020866:omega-Conotoxin GVIA; D000661:Amphetamine; C016299:chelerythrine; D011493:Protein Kinase C; D019311:Staurosporine; C070515:bisindolylmaleimide I; D011188:Potassium; D002118:Calcium; D004298:Dopamine