Comparison of pharmacological activities of Neuropeptide FF 1 and Neuropeptide FF 2 receptor agonists

Abstract

The pharmacological effects of Neuropeptide FF (NPFF) analogs exhibiting different selectivities towards Neuropeptide FF 1 (NPFF 1) and Neuropeptide FF 2 (NPFF 2) receptors were investigated after supraspinal administration in mice. Injected into the third ventricle, VPNLPQRF-NH 2, which is selective for Neuropeptide FF 1 receptor induced a hypothermia while EFWSLAAPQRF-NH 2 and SPAFLFQPQRF-NH 2 which are selective for Neuropeptide FF 2 receptor, did not. Furthermore, EFWSLAAPQRF-NH 2 significantly increased the body temperature when compared to saline treated mice, indicating that Neuropeptide FF 1 receptor could be responsible for hypothermia while Neuropeptide FF 2 mediated an hyperthermic effect. After administration into the lateral ventricle, 1DMe ([D.Tyr 1,(N.Me)Phe 3]NPFF), a weakly selective Neuropeptide FF 2 receptor agonist, exerted a clear anti-opioid effect in the tail flick test. The selective Neuropeptide FF 1 receptor agonist VPNLPQRF-NH 2 did not induce significant anti-opioid actions but rather increased, dose-dependently, morphine analgesia while EFWSLAAPQRF-NH 2, the highest selective Neuropeptide FF 2 receptor analog, induced the same pharmacological effect as VPNLPQRF-NH 2 at comparable doses. These features indicate that the pro- and anti-opioid actions are not strictly related to the selectivity towards Neuropeptide FF 2 or Neuropeptide FF 1 receptor. Our data demonstrate that Neuropeptide FF 1 and Neuropeptide FF 2 receptors differently modulate nervous system functions.