Nanomolar concentrations of cocaine enhance D2-like agonist-induced inhibition of the K+-evoked [3H]-dopamine efflux from rat striatal synaptosomes: a novel action of cocaine.
Previous studies have indicated that cocaine binding sites contain both high- and low-affinity binding components and have actions not related to dopamine uptake inhibition. Therefore, it has been studied if concentrations of cocaine in the range of 0.1-100 nM can affect not only dopamine uptake but also the quinpirole-induced inhibition of the K(+)-evoked [(3)H]-dopamine efflux from rat striatal synaptosomes. It was found that quinpirole-induced inhibition of K(+)-evoked [(3)H]-dopamine efflux was significantly enhanced by cocaine at 1 and 10 nM but not at 0.1 nM with cocaine alone being inactive and 1 nM cocaine lacking effects on [(3)H]-dopamine uptake in rat striatal synaptosomes. The results indicate the existence of a novel allosteric agonist action of cocaine in low concentrations, not affecting dopamine uptake, at striatal D(2) autoreceptors modulating striatal dopamine transmission.
Ferraro
Luca
L
Department of Experimental and Clinical Medicine, Section of Pharmacology and BioPharmaNet TransLab, University of Ferrara, 44100 Ferrara, Italy.
Beggiato
Sarah
S
Marcellino
Daniel
D
Frankowska
Malgorzata
M
Filip
Malgorzata
M
Agnati
Luigi F
LF
Antonelli
Tiziana
T
Tomasini
Maria C
MC
Tanganelli
Sergio
S
Fuxe
Kjell
K
D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D017660:Autoreceptors / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D008297:Male; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D013347:Subcellular Fractions; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
D017660:Autoreceptors; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D017448:Receptors, Dopamine D2; D014316:Tritium; D019257:Quinpirole; D003042:Cocaine; D011188:Potassium; D004298:Dopamine