Neuropeptide Y receptors involved in calcium channel regulation in PC12 cells

Our laboratory has previously used NGF-differentiated PC12 cells as a sympathetic neuronal model to investigate the effects of NPY on catecholamine synthesis and release. We have additionally used these cells to demonstrate the NPY-induced inhibition of Ca2+ channels which was suggested by those studies. In the present work, multiple NPY, PYY, and PP analogs are utilized to further define the receptor subtypes involved in this Ca2+ channel modulation. We find that in PC12 cells NPY and PP modulate Ca2+ channels through Y1, Y2, Y3, and Y4 receptors. In addition, we show that these receptors are differentially coupled to N, L, and non-N, non-L Ca2+ channel subtypes. The results of the present study in combination with our previous investigations demonstrate an intriguing and complex role for NPY and PP in the modulation of sympathetic neurotransmission.