Opposite alterations of NPFF1 and NPFF2 neuropeptide FF receptor density in the triple MOR/DOR/KOR-opioid receptor knockout mouse brains

Gouardères, Christine; Kieffer, Brigitte L.; Zajac, Jean‐Marie

doi:10.1016/j.jchemneu.2004.01.002

Cited by 8 publications

(6 citation statements)

References 33 publications

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“…Despite virtually no coexpression in GnRH neurons, strong Gpr74 expression was observed in the nucleus reunions (Fig. 8D) and nucleus accumbens, consistent with previous reports in mice (23,41,42).…”

Section: Experiments 6: Gpr147 Is Weakly Expressed In a Subset Of Gnrhsupporting

confidence: 91%

Development, Sex Steroid Regulation, and Phenotypic Characterization of RFamide-Related Peptide (Rfrp) Gene Expression and RFamide Receptors in the Mouse Hypothalamus

et al. 2012

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Arginine-phenylalanine-amide (RFamide)-related peptide 3 (RFRP-3, encoded by the Rfrp gene) is the mammalian ortholog of gonadotropin-inhibiting hormone and can inhibit GnRH neuronal activity and LH release. However, the development and regulation of the RFRP-3 system in both sexes is poorly understood. Using in situ hybridization, we examined changes in Rfrp-expressing neurons in mice of both sexes during development and under different adulthood hormonal milieus. We found no sex differences in Rfrp expression or cell number in adult mice. Interestingly, we identified two interspersed subpopulations of Rfrp cells (high Rfrp-expressing, HE; low Rfrp-expressing, LE), which have unique developmental and steroidal regulation characteristics. The number of LE cells robustly decreases during postnatal development, whereas HE cell number increases significantly before puberty. Using Bax knockout mice, we determined that the dramatic developmental decrease in LE Rfrp cells is not due primarily to BAX-dependent apoptosis. In adults, we found that estradiol and testosterone moderately repress Rfrp expression in both HE and LE cells, whereas the nonaromatizable androgen dihydrotestosterone has no effect. Using double-label in situ hybridization, we determined that approximately 25% of Rfrp neurons coexpress estrogen receptor-α in each sex, whereas Rfrp cells do not readily express androgen receptor in either sex, regardless of hormonal milieu. Lastly, when we looked at RFRP-3 receptors, we detected some coexpression of Gpr147 but no coexpression of Gpr74 in GnRH neurons of both intact and gonadectomized males and females. Thus, RFRP-3 may exert its effects on reproduction either directly, via Gpr147 in a subset of GnRH neurons, and/or indirectly, via upstream regulators of GnRH.

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Section: Experiments 6: Gpr147 Is Weakly Expressed In a Subset Of Gnrhsupporting

confidence: 91%

Development, Sex Steroid Regulation, and Phenotypic Characterization of RFamide-Related Peptide (Rfrp) Gene Expression and RFamide Receptors in the Mouse Hypothalamus

et al. 2012

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“…Furthermore, triple knockout mice for μ-, δ-, κ-opioids receptors (corresponding to MOR, DOR, and KOR, respectively) are hyperalgesic, which supports the idea that MOR/DOR/KOR deletion certainly affects the balance between opioid and anti-opioid systems, and then, may lead to an increase in NPFF system efficacy. Accordingly, MOR/DOR/KOR triple knockout mice showed an increase in NPFFR2 binding sites in several brain region and spinal cord ( 71 ). Finally, it has been shown that chronic i.c.v.…”

Section: Npff Rfrp and Npff Receptors 1/2mentioning

confidence: 99%

Involvement of Mammalian RF-Amide Peptides and Their Receptors in the Modulation of Nociception in Rodents

Ayachi¹,

Simonin²

2014

Front. Endocrinol.

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Mammalian RF-amide peptides, which all share a conserved carboxyl-terminal Arg–Phe–NH2 sequence, constitute a family of five groups of neuropeptides that are encoded by five different genes. They act through five G-protein-coupled receptors and each group of peptide binds to and activates mostly one receptor: RF-amide related peptide group binds to NPFFR1, neuropeptide FF group to NPFFR2, pyroglutamylated RF-amide peptide group to QRFPR, prolactin-releasing peptide group to prolactin-releasing peptide receptor, and kisspeptin group to Kiss1R. These peptides and their receptors have been involved in the modulation of several functions including reproduction, feeding, and cardiovascular regulation. Data from the literature now provide emerging evidence that all RF-amide peptides and their receptors are also involved in the modulation of nociception. This review will present the current knowledge on the involvement in rodents of the different mammalian RF-amide peptides and their receptors in the modulation of nociception in basal and chronic pain conditions as well as their modulatory effects on the analgesic effects of opiates.

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“…Given the widespread projections of RFRP-3 fibers and the dense expression of NPFF1R in the paraventricular nucleus (PVN), basolateral amygdala, lateral septum, and throughout the limbic system, it is likely that RFRP-3 has other roles in stress modulation that are yet to be elucidated (1,10,13). The stress-induced activation of the hypothalamic-pituitary adrenal (HPA) axis is dependent on corticotropin-releasing hormone (CRH) neurons in the PVN, which stimulate the release of adrenocorticotropic hormone from the anterior pituitary gland.…”

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confidence: 99%

“…Acute exposure to elevated corticosterone alone is sufficient to induce anxiety and cause dendritic hypertrophy in the basolateral amygdala (37). NPFF1R is broadly distributed in the brain but is particularly densely expressed in the PVN, brainstem, basolateral, central, and medial amygdala, lateral septum, bed nucleus of stria terminalis, and ventral tegmental area (1,10,13,38); all of which are known to play a role in the regulation of fear-, depression-, and/or anxiety-related behaviors. It is important to note that our behavioral studies come from female mice only, whereas the data for corticosterone measurements and CRH neuronal activation were males.…”

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confidence: 99%

Anxiogenic and Stressor Effects of the Hypothalamic Neuropeptide RFRP-3 Are Overcome by the NPFFR Antagonist GJ14

et al. 2015

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RFamide-related peptide-3 (RFRP-3) is a recently discovered neuropeptide that has been proposed to play a role in the stress response. We aimed to elucidate the role of RFRP-3 and its receptor, neuropeptide FF (NPFF1R), in modulation of stress and anxiety responses. To achieve this, we characterized a new NPFF1R antagonist because our results showed that the only commercially available putative antagonist, RF9, is in fact an agonist at both NPFF1R and the kisspeptin receptor (KISS1R). We report here the identification and pharmacological characterization of GJ14, a true NPFFR antagonist. In in vivo tests of hypothalamic-pituitary-adrenal (HPA) axis function, GJ14 completely blocked RFRP-3-induced corticosterone release and neuronal activation in CRH neurons. Furthermore, chronic infusion of GJ14 led to anxiolytic-like behavior, whereas RFRP-3 infusion had anxiogenic effects. Mice receiving chronic RFRP-3 infusion also had higher basal circulating corticosterone levels. These results indicate a stimulatory action of RFRP-3 on the HPA axis, consistent with the dense expression of NPFF1R in the vicinity of CRH neurons. Importantly, coinfusion of RFRP-3 and GJ14 completely reversed the anxiogenic and HPA axis-stimulatory effects of RFRP-3. Here we have established the role of RFRP-3 as a regulator of stress and anxiety. We also show that GJ14 can reverse the effects of RFRP-3 both in vitro and in vivo. Infusion of GJ14 causes anxiolysis, revealing a novel potential target for treating anxiety disorders.

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Opposite alterations of NPFF1 and NPFF2 neuropeptide FF receptor density in the triple MOR/DOR/KOR-opioid receptor knockout mouse brains

Cited by 8 publications

References 33 publications

Development, Sex Steroid Regulation, and Phenotypic Characterization of RFamide-Related Peptide (Rfrp) Gene Expression and RFamide Receptors in the Mouse Hypothalamus

Development, Sex Steroid Regulation, and Phenotypic Characterization of RFamide-Related Peptide (Rfrp) Gene Expression and RFamide Receptors in the Mouse Hypothalamus

Involvement of Mammalian RF-Amide Peptides and Their Receptors in the Modulation of Nociception in Rodents

Anxiogenic and Stressor Effects of the Hypothalamic Neuropeptide RFRP-3 Are Overcome by the NPFFR Antagonist GJ14

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