N-acyldopamines control striatal input terminals via novel ligand-gated cation channels.
Endogenous analogues of capsaicin, N-acyldopamines, were previously identified from striatal extracts, but the putative presynaptic role of their receptor, the TRPV(1)R (formerly: vanilloid or capsaicin receptor) in the caudate-putamen is unclear. We found that the endogenous TRPV(1)R agonists, N-arachidonoyldopamine (NADA) and oleoyldopamine (OLDA) with EC(50) values in the nanomolar range, as well as the synthetic TRPV(1)R activator 2-aminoethoxydiphenylborane (2APB), and palmytoyldopamine (PALDA, another endogenous N-acyldopamine inactive at the TRPV(1)R), but not capsaicin or other endogenous and synthetic cannabinoids, triggered a rapid Ca(2+) entry with the concomitant stimulation of glutamate and dopamine release. These effects persisted in the TRPV(1)R null-mutant mice, and were insensitive to antagonists of common ionotropic receptors, to several TRPV(1)R antagonists and to the absence of K(+). Furthermore, these N-acyldopamine receptors in glutamatergic and dopaminergic terminals are different based on their different sensitivity to anandamide, capsazepine and Gd(3+) at nanomolar concentrations. Altogether, novel ion channels instead of the TRPV(1)R mediate the presynaptic action of N-acyldopamines in the striatum of adult rodents.
Ferreira
Samira G
SG
Center for Neuroscience and Cell Biology of Coimbra, Department of Zoology, Faculty of Medicine, University of Coimbra, 1 Rua Larga, 3004-504 Coimbra, Portugal.
Lomaglio
Tonia
T
Avelino
Antonio
A
Cruz
Francisco
F
Oliveira
Catarina R
CR
Cunha
Rodrigo A
RA
Köfalvi
Attila
A
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001896:Boron Compounds / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002412:Cations; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D063388:Endocannabinoids; D018698:Glutamic Acid / Q000378:metabolism; D007473:Ion Channels; D008024:Ligands; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000378:metabolism; D050916:TRPV Cation Channels / Q000819:agonists
C504876:2-aminoethoxydiphenylborane; D001095:Arachidonic Acids; D001896:Boron Compounds; D002412:Cations; D063388:Endocannabinoids; D007473:Ion Channels; D008024:Ligands; D053284:Polyunsaturated Alkamides; D050916:TRPV Cation Channels; C474941:arachidonyl dopamine; D018698:Glutamic Acid; C071423:capsazepine; D002211:Capsaicin; C078814:anandamide; D004298:Dopamine