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Neuropeptide FF (NPFF) is a peptide expressed in the brain and spinal cord that shares a precursor protein with neuropeptide AF. NPFF is expressed primarily in the posterior pituitary, hypothalamus, and medulla. It is an agonist at NPFF1 and NPFF2 receptors (K_is = 2.82 and 0.21 nM, respectively, for human recombinant receptors) that inhibits forskolin-induced cAMP production in CHO cells (EC₅₀s = 236 and 2.3 nM, respectively). NPFF activates parvocellular neurons in the paraventricular nucleus (PVN) of the hypothalamus to stimulate oxytocin release from their projections in the brain stem, thereby regulating baroreflex control of heart rate. However, it inhibits magnocellular PVN neurons by enhancing GABAergic input. It is also found in plasma and exogenous administration briefly increases mean arterial pressure (MAP) by 40 mm Hg in rats, an effect that is only partially blocked by the norepinephrine competitor guanethidine and the α₁-adrenergic receptor antagonist prazosin . NPFF has anti-opioid effects in rodent models, inhibiting morphine-induced analgesia and inducing abstinence in morphine-tolerant rats. It also inhibits acquisition of conditioned place preference to cocaine in rats when administered at doses of 10 and 20 nmol.

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Endogenous antiopioid peptide and agonist at NPFF1 and NPFF2 receptors (Ki values are 2.82 and 0.21 nM respectively). Exhibits anorexigenic effects.

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