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 TRPV1R (formerly: vanilloid or capsaicin receptor) in the caudate-putamen is unclear. We found that the endogenous TRPV1R agonists, N-arachidonoyldopamine (NADA) and oleoyldopamine (OLDA) with EC50 values in the nanomolar range, as well as the synthetic TRPV1R activator 2-aminoethoxydiphenylborane (2APB), and palmytoyldopamine (PALDA, another endogenous N-acyldopamine inactive at the TRPV1R), but not capsaicin or other endogenous and synthetic cannabinoids, triggered a rapid Ca2+ entry with the concomitant stimulation of glutamate and dopamine release. These effects persisted in the TRPV1R null-mutant mice, and were insensitive to antagonists of common ionotropic receptors, to several TRPV1R 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 Gd3+ at nanomolar concentrations. Altogether, novel ion channels instead of the TRPV1R mediate the presynaptic action of N-acyldopamines in the striatum of adult rodents.