Neuropeptide FF

Neuropeptide FF (NPFF), an octapeptide belonging to the RF-amide family of peptides, is a NPFF1 and NPFF2 receptors agonist with K_i values of 2.82 nM and 0.21 nM, respectively. Neuropeptide FF induces abstinence syndrome, exerts antiopioid and analgesic effects, releases via calcium-dependent mechanisms from rat spinal cord, regulates memory, autonomic function, and neuroendocrine function, modulates pain and opioid antinociception, reduces food intake, stimulates water intake, alters cardiovascular parameters, and shows differential activity in hypothalamic paraventricular nucleus neurons. Neuropeptide FF is present in mammalian central nervous system and periphery, with NPFF-immunoreactivity increases in rat cerebrospinal fluid during opiate tolerance, and its NPFF gene and NPFF-R2 gene are up-regulated in rat spinal cord and dorsal root ganglia during peripheral inflammation. Neuropeptide FF can be used for the research of opioid tolerance, morphine-induced analgesia, abstinence syndrome, pain, hypertension, nociception, inflammatory pain, and neuropathic pain^{[1][2][3][4][5][6][7]}. In Vitro:Neuropeptide FF (0.1 pM-100 nM) exerts concentration-dependent effects on human peripheral blood lymphocyte proliferation, enhancing proliferation at 0.1 pM and inhibiting proliferation at 100 nM^[1].
Neuropeptide FF binds to two distinct sites on human Jurkat T lymphocyte cells, with a high-affinity site (K_d of 0.29 nM) and a low-affinity site (K_d of 0.512 μM)^[1].
Neuropeptide FF binds with high affinity to both human NPFF-R1 and NPFF-R2 expressed in CHO-NFA-bla cells, with a slightly higher affinity for NPFF-R2 (IC₅₀ = 3.1 nM) compared to NPFF-R1 (IC₅₀ = 6.2 nM)^[3].
Neuropeptide FF specifically potentiates acid-gated currents in Xenopus oocytes expressing heteromeric human ASIC2a + ASIC3 channels by delaying channel desensitization^[3].
Neuropeptide FF reduces depolarization-induced intracellular calcium elevation in dissociated mouse dorsal root ganglion neurons^[3].
Neuropeptide FF (NPFF) (0.01-10 μM; 5 min) dose-dependently activates ERK phosphorylation in dSH-SY5Y cells via a PKA-, inducible nitric oxide synthase-, and neuronal nitric oxide synthase-dependent mechanism, with peak activation at 10 μM for 5 min^[4].
Neuropeptide FF (NPFF) (0.01-10 μM; 90-135 min) activates the upstream components of the NF-κB pathway in dSH-SY5Y cells in a time- and dose-dependent, ERK-independent manner, with peak IKKα/β phosphorylation at 10 μM for 120 min and peak I-κKα phosphorylation at 10 μM for 135 min^[4]. In Vivo:Neuropeptide FF (intracerebroventricular; intrathecal; focal brainstem microinjection) modulates cardiovascular function via dose-dependent changes in blood pressure, heart rate, and selective activation/inhibition of hypothalamic and brainstem neurons, and blunts hypovolemia-induced vasopressin release in rats^[2].
Neuropeptide FF (intrathecal) produces potent antiallodynia in rats with carrageenan-induced inflammatory nociception^[3].
Neuropeptide FF (intrathecal) produces potent antiallodynia in rats with mononeuropathic or diabetic neuropathic nociception^[3].
Neuropeptide FF (NPFF) (5-10 μg/rat; i.c.v.; single injection) produces a dose-related reduction in food intake during the first 60 minutes in 24-hour food-deprived male Sprague-Dawley rats, with the 10 μg/rat dose inducing a statistically significant decrease^[5].