Disease relevance of Npffr1

• In culture, RFRP-1 lowered cAMP production in Chinese hamster ovary cells expressing OT7T022 and it was abolished by pre-treatment with pertussis toxin, suggesting that OT7T022 couples G(i)/G(o) in the signal transduction pathway [1].
• Neuropeptide FF (NPFF), an FMRFamide-like peptide with antiopioid properties, inhibits morphine-induced analgesia but also produces hyperalgesia [2].
• The plasma AVP increase in response to PEG-induced hypovolemia was also attenuated significantly and more potently when NPFF was injected into the cisterna magna so that the given drug could be readily accessible to the dorsal medulla where the nucleus of solitary tract is located (10 micrograms/rat; 2.71 +/- 0.14 pg/ml) [3].
• The up-regulation of NPFF may play a homeostatic role in response to specific cardiovascular challenges, such as hypotension [4].

Psychiatry related information on Npffr1

• When injected in the VTA, NPFF is acting as an antiopioid compound, i.e. it reduces the locomotor activity triggered by exposure to novelty to the level recorded in a familiar environment [5].
• Previous studies suggest that neuropeptide FF (NPFF) plays a role in opiate dependence and subsequent abstinence syndrome [6].
• The results suggest that NPFF may modulate the neuronal process of amphetamine addiction [7].
• The NPFF analog, desamino YFLFQPQRamide (daY8Ra) has previously antagonized behavioral effects of NPFF and has attenuated morphine dependence [6].

High impact information on Npffr1

• These similarities together with the finding that BIBP3226, an anorexigenic Y1 receptor ligand, also binds to NPFF1 suggest a potential role for NPFF1 in feeding [8].
• Neuropeptide FF (NPFF) is involved in pain modulation, especially plasticity during inflammatory and neuropathic pain, and opiate interactions [9].
• These results suggest that central NPFF might play an inhibitory role via the hypothalamus in the osmoregulation of plasma AVP and via both the hypothalamus and the nucleus of solitary tract in the baroregulation, and that the intrinsic opioid systems are involved in the action of NPFF [3].
• In contrast, the NPFF injected into the cisterna magna had no significant effect on hyperosmolality-induced AVP release [3].
• In the present study, the mechanisms of NPFF release were investigated in an in vitro superfusion system with rat spinal cord slices [2].

Biological context of Npffr1

• In the rat spinal cord, gene expression of NPFF but not that of NPVF was up-regulated by persistent pain induced by carrageenan inflammation [10].
• Our data suggest that 125I-Y8Fa binding sites in rat CNS are G protein-coupled NPFF receptors regulated by GTP and cations [11].
• Conscious rats received saline or NPFF (8 or 10 microg i.c.v.), with concomitant monitoring of arterial blood pressure [4].
• Surprisingly, the alpha2 adrenergic receptor antagonists, idazoxan (2 mg/kg, i.v.) and yohimbine (2 mg/kg, i.v.), both produced a drastic increase in the NPFF-induced heart rate response [12].
• These results indicate that NPFF modulates excitatory synaptic transmission in the PBN through an interaction with presynaptic delta-opioid receptors [13].

Anatomical context of Npffr1

• To further explore the functional role of PQRF-NH(2) peptides, we have studied their distribution and also the regulation of NPFF and NPVF systems in the spinal cord of rats with peripheral inflammation [10].
• The mechanism of inhibition in spinal cord membranes appeared to be a reduction in the number of NPFF receptors; in one experiment, control KD and Bmax values were 0.068 nM and 7.2 fmol/mg of protein, respectively, and with 0.1 microM guanylylimidodiphosphate the respective values were 0.081 nM and 4.9 fmol/mg, a 32% reduction in receptor number [11].
• NPFF fibers and cells have been shown to be discretely localized in key autonomic centers within the brain, including the brainstem nucleus of the solitary tract (NTS) [4].
• Specific receptors for the octapeptide FLFQPQRFamide (NPFF), a mammalian FMRFamide-like neuropeptide with anti-opiate properties have been identified in rat central nervous system [14].
• Significantly greater numbers of activated neurons expressing the NPFF gene (double labeled) were observed in the NTS at the level of the area postrema in animals receiving i.c.v. NPFF compared with saline controls [4].

Associations of Npffr1 with chemical compounds

• Several lines of evidence suggest that neuropeptide FF (NPFF) is involved in nociception and in the modulation of opioid-mediated analgesia [10].
• In contrast, the presence of a glycine residue in position 5 did not influence the affinity toward NPFF receptors [15].
• We found that NaCl (but not KCl or LiCl) and MgCl2 increased specific 125I-YLFQPQRFamide (125I-Y8Fa) binding to NPFF receptors in both tissues in a dose-dependent manner, with optimal conditions being 60 mM NaCl and 1 mM MgCl2 [11].
• NPFF neurons activated during NP infusion constituted the largest number of cells projecting to the PBN [16].
• Intravenous administration of NPFF (100-300 micrograms/kg) produced a dose-dependent increase in blood pressure and heart rate without affecting plasma noradrenaline and adrenaline levels [12].

Analytical, diagnostic and therapeutic context of Npffr1

• The presence of NPFF receptors on heart sections and of NPFF-immunoreactivity in heart tissue was demonstrated with autoradiographic and radioimmunoassay procedures, respectively [12].
• Activated NTS neurons were identified by using a combined immunohistochemistry for Fos and NPFF, and neurons projecting to the PBN were determined with a retrograde tracer [16].
• Measurements by quantitative receptor autoradiography in the superficial layers of the spinal cord revealed that NPFF analogs tested have only a low affinity for opioid receptors since Ki values ranged from 5 to 400 microM [17].
• Similar cardiovascular effects were observed after bilateral NTS microinjections of one analog neuropeptide FF receptor agonist, [DTyr1, (NMe)Phe3]NPFF (1 nmol) [18].
• High performance liquid chromatography analysis of adrenal extracts revealed a single molecular form which coeluted with authentic NPFF [19].

References