The effects of neuropeptide S on general anesthesia in rats.

BACKGROUND: Neuropeptide S (NPS) and its receptor (NPSR) is a novel neuropeptide system that regulates arousal and anxiety. A link between natural sleep and general anesthesia has been suggested. Therefore, we hypothesized that the NPS neuronal system may also modulate general anesthesia. METHODS: The effects of intracerebroventricular NPS and [D-Cys(tBu)(5)]NPS, a peptide NPSR antagonist, on ketamine and thiopental anesthesia time were measured in rats. Anesthesia time was defined as the interval between the loss of righting reflex and its recovery. RESULTS: Intracerebroventricular NPS 1 to 30 nmol significantly reduced ketamine anesthesia time, showing a bell-shaped dose-response curve. [D-Cys(tBu)(5)]NPS 20 nmol antagonized NPS 1 nmol effects and was per se able to increase ketamine anesthesia time. Similar results were obtained investigating thiopental anesthesia time that was significantly reduced by NPS and prolonged by [D-Cys(tBu)(5)]NPS. CONCLUSION: NPS via selective NPSR activation stimulates the wakefulness-promoting pathway, thus reducing anesthesia duration. The endogenous NPS/NPSR system seems to tonically control these pathways

The effects of neuropeptide S on general anesthesia in rats

BACKGROUND: Neuropeptide S (NPS) and its receptor (NPSR) is a novel neuropeptide system that regulates arousal and anxiety. A link between natural sleep and general anesthesia has been suggested. Therefore, we hypothesized that the NPS neuronal system may also modulate general anesthesia. METHODS: The effects of intracerebroventricular NPS and [D-Cys(tBu)(5)]NPS, a peptide NPSR antagonist, on ketamine and thiopental anesthesia time were measured in rats. Anesthesia time was defined as the interval between the loss of righting reflex and its recovery. RESULTS: Intracerebroventricular NPS 1 to 30 nmol significantly reduced ketamine anesthesia time, showing a bell-shaped dose-response curve. [D-Cys(tBu)(5)]NPS 20 nmol antagonized NPS 1 nmol effects and was per se able to increase ketamine anesthesia time. Similar results were obtained investigating thiopental anesthesia time that was significantly reduced by NPS and prolonged by [D-Cys(tBu)(5)]NPS. CONCLUSION: NPS via selective NPSR activation stimulates the wakefulness-promoting pathway, thus reducing anesthesia duration. The endogenous NPS/NPSR system seems to tonically control these pathways

Effects of nociceptinNH(2) and [Nphe(1)]nociceptin(1-13)NH2 on rat brain noradrenaline release in vivo and in vitro

none8We have investigated the effects of nociceptin/orphanin FQ (NC) receptor agonist NCNH2 and a competitive NC receptor antagonist, [Nphe1]NC(1±13)NH2 on noradrenaline (NA) release in vivo using microdialysis in freely moving animals and in vitro from cerebrocortical slices. One nmol of NCNH2 injected into rat locus coeruleus inhibited NA release from the prefrontal cortex (Emax 27.4 ^ 5.7% 30 min after injection) which was partially (33%) reversed by 100 nmol of [Nphe1]NC(1±13)NH2. In cerebrocortical slices NCNH2 inhibited NA release in a concentration-dependent manner (EC50 12 nM, Emax 29.4%) that was reversed by [Nphe1]NC(1±13)NH2. In both preparations, [Nphe1]NC(1±13)NH2 per se was inactive. These data demonstrate an inhibition of NA release by NCNH2 in a [Nphe1]NC(1±13)NH2 sensitive manner in both in vivo brain microdialysis and in vitro cerebrocortical slices studies in rats.mixedOKAWA H; KUDO M; KUDO T; R. GUERRINI; LAMBERT DG; KUSHIKATA T; YOSHIDA H; MATSUKI AOkawa, H; Kudo, M; Kudo, T; Guerrini, Remo; Lambert, Dg; Kushikata, T; Yoshida, H; Matsuki, A

Urotensin II evokes neurotransmitter release from rat cerebrocortical slices.

Urotensin II (UII) has been reported to modulate rapid eye movement (REM) sleep via activation of brainstem cholinergic neurons and REM sleep is regulated by locus coerleus (LC)–cerebrocortical noradrenergic neurons. We hypothesized that UII may activate LC–cerebrocortical noradrenergic neurons. To test this hypothesis, we have examined the effects of UII on norepinephrine release from rat cerebrocortical slices. In addition, the effect of the putative UT receptor antagonist [Pen5, DTrp7, Dab8]UII(4–11) (UFP-803) was assessed. We have compared this with other wakefulness-promoting neurotransmitters such as dopamine, glutamate, serotonin and histamine. We also studied the effects of UII and UFP-803 on intracellular Ca2+ ([Ca2+]i) in HEK293 cells stably expressing rat UT receptor (HEK293-rUT cells). UII produced a time- (peaking at 10 min following stimulation with 10 nM) and concentration-dependent increase in norepinephrine release with pEC50 and Emax (% of basal) values of 8.78 ± 0.17 (1.65 nM) and 138 ± 2%, respectively. UII also evoked dopamine, serotonin and histamine release with similar pEC50 values. UII increased glutamate release but only at high concentrations (<100 nM) and this failed to saturate. UII markedly increased [Ca2+]i in HEK293-rUT cells in a concentration-dependent manner with pEC50 of 8.26 ± 0.24. The UT antagonist UFP-803 reversed both UII-increased norepinephrine release from the cerebrocortical slices (pKB = 8.98) and [Ca2+]i (pKB = 8.87) in HEK293-rUT cells. Collectively these data suggest that UII evokes the release of norepinephrine via UT receptor activation and produces similar effects on other wakefulness-promoting neurotransmitters: these neurochemical actions of UII may be important for the control of the sleep–wake cycle

Central noradrenergic activity affects analgesic effect of Neuropeptide S

Background Neuropeptide S (NPS) is an endogenous neuropeptide controlling anxiolysis, wakefulness, and analgesia. NPS containing neurons exist near to the locus coeruleus (LC) involved in the descending anti-nociceptive system. NPS interacts with central noradrenergic neurons; thus brain noradrenergic signaling may be involved in NPS-induced analgesia. We tested NPS analgesia in noradrenergic neuron-lesioned rats using a selective LC noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). Methods A total 66 male Sprague–Dawley rats weighing 350–450 g were used. Analgesic effects of NPS were evaluated using hot-plate and tail-flick test with or without DSP-4. The animal allocated into 3 groups; hot-plate with NPS alone intracerebroventricular (icv) (0.0, 1.0, 3.3, and 10.0 nmol), tail-flick NPS alone icv (0.0 and 10.0 nmol), and hot-plate with NPS and DSP-4 (0 or 50 mg/kg ip). In hot-plate with NPS and DSP-4 group, noradrenaline content in the cerebral cortex, pons, hypothalamus, were measured. Results NPS 10 nmol icv prolonged hot plate (%MPE) but not tail flick latency at 30 and 40 min after administration. DSP-4 50 mg/kg decreased noradrenaline content in the all 3 regions. The NA depletion inhibited NPS analgesic effect in the hot plate test but not tail flick test. There was a significant correlation between hot plate latency (percentage of maximum possible effect: %MPE) with NPS 10 nmol and NA content in the cerebral cortex (p = 0.017, r 2 = 0.346) which noradrenergic innervation arisen mainly from the LC. No other regions had the correlation. Conclusions NPS analgesia interacts with LC noradrenergic neuronal activity