NEUROPEPTIDE-Y INHIBITS CA2+ INFLUX INTO CULTURED DORSAL-ROOT GANGLION NEURONS OF THE RAT VIA A Y2 RECEPTOR

1 The identity of the neuropeptide Y (NPY) receptor associated with the observed inhibition of neuronal Ca2+ currents (I(Ca)) in rat dorsal root ganglion (DRG) cells has been established on the basis of agonist responses to analogues and carboxy terminal (C-terminal) fragments of the NPY molecule. 2 Whole cell barium currents (I(Ba)) in DRG cells were reversibly inhibited by 100 nM NPY, 100 nM PYY and C-terminal fragments of NPY in a manner that correlated with the length of the NPY fragments (for inhibition of the I(Ba) NPY = PYY > NPY2-36 > NPY13-36 > NPY16-36 > NPY18-36 >>> NPY25-36). 3 C-terminal fragments of NPY were also effective in reversibly reducing the I(Ca), the associated increase in the intracellular Ca2+ concentration ([Ca2+]i) and the increased [Ca2+]i produced by evoked action potentials in the DRG cells. In addition, a Ca2+-activated Cl- conductance was also reversibly reduced by NPY fragments only when accompanied by a reduction in Ca2+ entry. 4 We conclude that the Y2 receptor for neuropeptide Y is coupled to inhibition of Ca2+ influx via voltage-sensitive calcium channels in DRG cells.