The role of the NOP receptor in regulating food intake, meal pattern, and the excitability of proopiomelanocortin neurons.
We evaluated the role of the nociceptin/orphanin FQ (NOP) receptor in regulating food intake, meal pattern and the activity of hypothalamic arcuate (ARC) neurons. The microstructural analysis of food intake and meal pattern was performed under both food-deprived and ad libitum conditions. Whole-cell patch clamp recordings were obtained using the in vitro hypothalamic slice preparation and biocytin-filled electrodes. NOP receptor knockout mice exhibited significantly reduced body weight. Fasting-induced hyperphagia was diminished for the first 2h of a 6-h re-feeding period, and was associated with decreased meal duration and size, as well as a biphasic effect on meal frequency. The genotype effect observed under ad libitum conditions was comparatively unremarkable. Orphanin FQ/nociceptin (OFQ/N) was able to decrease evoked excitatory postsynaptic current amplitude, increase the S(2):S(1) ratio via the paired-pulse paradigm, and decrease miniature excitatory postsynaptic current frequency in ARC neurons from wild type animals but not NOP receptor knockouts. In addition OFQ/N activated a reversible outward current that was antagonized by the G-protein activated, inwardly-rectifying K(+) (GIRK) channel blocker tertiapin in wild type but not NOP knockout animals. Both the presynaptic and postsynaptic actions of OFQ/N were observed in ARC neurons subsequently determined to be immunopositive for characteristic phenotypic markers of anorexigenic proopiomelanocortin (POMC) neurons. Taken together, these results demonstrate the contribution of the NOP receptor in controlling food intake and meal pattern, as well as glutamate release and GIRK1 channel activity at POMC synapses.
College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766, USA.
Borzoo
B
Farhang
Lindsay
L
Pietruszewski
Kabirullah
K
Lutfy
Edward J
EJ
Wagner
D000704:Analysis of Variance; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects / Q000235:genetics*; D001703:Biophysics; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018847:Opioid Peptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D011957:Receptors, Opioid / Q000172:deficiency / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018847:Opioid Peptides; D011333:Pro-Opiomelanocortin; D011957:Receptors, Opioid; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722287:Oprl1 protein, mouse