Neuropeptide Y inhibits Ca²+ influx into cultured dorsal root ganglion neurones of the rat via a Y₂ receptor

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. 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). 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. We conclude that the Y₂ receptor for neuropeptide Y is coupled to inhibition of Ca²⁺ influx via voltage‐sensitive calcium channels in DRG cells. 1991 British Pharmacological Society