Influence of a carrier transport process on in vivo release and metabolism of dopamine: dependence on extracellular Na+.
In vivo microdialysis was utilized to evaluate the role of extracellular Na+ in regulating dopamine (DA) neurotransmission in the caudate-putamen of halothane-anaesthetized rats. Reduction of the extracellular Na+ concentration by introduction of a perfusion media containing 50mM Na+ (with choline replacement) produced an excessive release of DA that could be effectively blocked by nomifensine and Lu 19-005, potent inhibitors of an amine transport carrier. These results substantiate reports of a carrier-mediated efflux of DA from presynaptic terminals. Pretreatment with amphetamine, considered both a DA uptake inhibitor and releaser, did not, however, influence the efflux of DA induced by the low extracellular Na+ environment. Although the release of DA from an apparent non-granular cytosolic pool was greatly enhanced by the low extracellular Na+ environment, 3,4-dihydrophenylacetic acid (DOPAC) levels, which supposedly reflect metabolism of non-vesicular DA, were minimally effected. In contrast, homovanillic acid (HVA) was sensitive to extracellular Na+ and not directly related to extracellular levels of either DA or DOPAC, suggesting the possibility of a Na+-sensitive (carrier-mediated?) process involved in the formation of HVA. Overall, the results of this paper cannot be completely reconciled with the traditional concept of intracellular organization of DA pools and suggests the possibility of various non-granular pools being differentially sensitive to efflux and metabolism.
Hurd
Y L
YL
Karolinska Institute, Department of Pharmacology, Stockholm, Sweden.
Ungerstedt
U
U
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D007189:Indans / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009627:Nomifensine / Q000494:pharmacology; D010477:Perfusion; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology / Q000502:physiology*; D009435:Synaptic Transmission
D007189:Indans; D015102:3,4-Dihydroxyphenylacetic Acid; D009627:Nomifensine; C045117:Lu 19005; D012964:Sodium; D003913:Dextroamphetamine; D004298:Dopamine; D006719:Homovanillic Acid