Neuropeptide FF (NPFF) agonists counteract the cellular opioid actions. We demonstrate for the first time a biochemical anti-opioid effect of NPFF receptors in the rat spinal cord by using the [(35)S]GTPgammaS binding assay in autoradiography. The mu agonist DAMGO as well as the potent and selective NPFF(2) agonist dNPA, stimulated [(35)S]GTPgammaS binding at different optimal GDP concentrations. dNPA decreased the effects induced by DAMGO alone; the maximal of G-protein coupling was decreased but not the potency of opioid agonist. We conclude that NPFF(2) receptors are coupled to G-protein in the rat spinal cord and could exert a molecular anti-opioid effect.
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