Ca2+ dependence of the amphetamine, nomifensine, and Lu 19-005 effect on in vivo dopamine transmission.
The present in vivo microdialysis study examined the role of vesicular- and carrier-mediated mechanisms underlying dopamine (DA) release, uptake and metabolism in halothane-anaesthetized rats. Omission of calcium (Ca2+) from the dialysis perfusing medium, thereby reducing the concentration of Ca2+ in the striatal microenvironment necessary for vesicular DA release, attenuated the elevation of DA normally induced by the potent DA uptake inhibitors, nomifensine and Lu 19-005. Consistent with the results of in vitro studies, amphetamine release DA in a Ca2+-independent manner. The release of DA induced by amphetamine could be effectively blocked by nomifensine and Lu 19-005, demonstrating that the in vivo movement of amines occurred via a transport carried-mediated mechanism. Additionally, the inhibition of DA metabolism produced by amphetamine could be reversed or blocked by prior or delayed treatment with DA uptake inhibitors. The results support a bidirectional in vivo capability of the amine transport carrier.
Hurd
Y L
YL
Karolinska Institute, Pharmacology Department, Stockholm, Sweden.
Ungerstedt
U
U
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology*; D007192:Indenes / Q000494:pharmacology*; D008297:Male; D009627:Nomifensine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
D007189:Indans; D007192:Indenes; D015102:3,4-Dihydroxyphenylacetic Acid; D009627:Nomifensine; C045117:Lu 19005; D000661:Amphetamine; D002118:Calcium; D004298:Dopamine; D006719:Homovanillic Acid