Opposite alterations of NPFF1 and NPFF2 neuropeptide FF receptor density in the triple MOR/DOR/KOR-opioid receptor knockout mouse brains.
Mice lacking the mu-delta-kappa-opioid receptor (MOR/DOR/KOR) genes and their corresponding wild-type littermates have been used to quantify NPFF(1) and NPFF(2) (neuropeptide FF) receptors by in vitro autoradiography in the central nervous tissues. Adjacent coronal sections were labelled with [125I]YVP ([125I]YVPNLPQRF-NH(2)) and [125I]EYF ([125I]EYWSLAAPQRF-NH(2)) as specific radioligands for NPFF(1) and NPFF(2) receptors, respectively. NPFF(2) receptors are predominantly expressed in both genotypes, but their density increases significantly in non cortical regions of mutant mice: 64% in the amygdaloid area, 89, 308, 1214 and 49% in the nucleus of the vertical limb of the diagonal band, substantia nigra, the vestibular nucleus and the spinal cord, respectively. In contrast, the density of the NPFF(1) subtype is lower than NPFF(2) in both genotypes and significantly decreased in some brain areas of mutant mice: -99, -90 and -90% in the nucleus of the vertical limb of the diagonal band, substantia nigra and the spinal cord, respectively. This study shows that mice lacking opioid receptors have brain region-dependent increases (NPFF(2)) and decreases (NPFF(1)) in NPFF receptors densities and suggests a different functional participation of each NPFF receptor subtype in the actions of opioids.
Gouardères
Christine
C
Institut de Pharmacologie et de Biologie Structurale, C.N.R.S. UMR 5089, 205 Route de Narbonne, 31077 Toulouse Cedex, France.
Kieffer
Brigitte L
BL
Zajac
Jean-Marie
JM
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D011957:Receptors, Opioid / Q000172:deficiency* / Q000235:genetics; D017465:Receptors, Opioid, delta / Q000172:deficiency / Q000235:genetics; D017473:Receptors, Opioid, kappa / Q000172:deficiency / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000172:deficiency / Q000235:genetics
D018013:Receptors, Neuropeptide; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C083929:neuropeptide FF receptor