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Orexin-A in rat hindbrain stimulates gastric motor function
OREXIN-A IN RAT HINDBRAIN STIMULATES GASTRIC MOTOR FUNCTION Hornby, Pamela J; Krowicki, Zbigniew K; Fuchs, Kristine M; Berthoud, Hans- R LSU-HSC, New Orleans, USA Orexins are neuropeptides that regulate food intake. Recently it was reported that fourth ventricular administration of orexin-A stimulates vagally-dependent gastric acid secretion in conscious rats (Biochem Siophys Res Communl999:254, 623). Therefore, we tested the hypothesis that orexin-A regulates gastric motor function via the vagal nuclei, which are the dorsal vagal complex (DVC) and the nucleus ambiguus (nAmb) in rats. To do this we used antibodies to orexin-A and its receptor (ORI; Alpha Diagnostic, San Antonio TX) for immunocytochemical analysis and microinjection of orexin-A (100 pmol) into the DVC and nAmb to determine the effects on gastric motor function in anesthetized rats. Orexin-A immunoreactive fibers are sparse to moderately represented in nucleus tractus solitarius, with very few fibers traversing the DMN. Consistent with the distribution of the endogenous ligand, OR1 staining is sparse to moderately expressed in these regions. Both orexin-A and ORl-immunoreactive staining are present in the nucleus ambiguus and para-ambigual regions of the reticular formation. Microinjection of orexin-A into the DVC (N=6) did not significantly alter intragastric pressure (+2.3*1.7 cmH20) or antral motility index (+I .7*1.2 MMI) compared to vehicle. In contrast, microinjection of orexin-A (N=6) into the vicinity of the nAmb significantly increased peak intragastric pressure (+ 3.3*1 .l cmHzO, P
OREXINS INCREASE ACTIVE BEHAVIOUR AND CNS OREXIN A IMMUNOREACTIVITY IS SIGNIFICANTLY DIFFERENT BETWEEN SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS Taheri, Shahrad; Sunter, David; Hafizi, Sepehr; Dakin, Catherine; Murphy, Kevin; Ghatei, Mohammad; Bloom, Stephen Imperial College School of Medicine, London, United Kingdom Orexins (A and B), neuropeptides synthesised in the dorsolateral hypothalamus, have been implicated in the regulation of arousal and the sleep/wake cycle. We administered orexins into the third ventricle of Wistar rats in the early light phase and observed animal behaviour over the next 24 hours, In the first 4 hours postinjection, orexins significantly increased active behaviour such as locomotion, grooming and burrowing. In the subsequent 20 hours, orexin A resulted in reduced activity and increased still behaviour, suggesting a disruption in the circadian pattern of activity. Using a sensitive and specific radioimmunoassay for orexin A, we studied orexin A immunoreactivity (orexin A-IR) in discrete CNS regions of 12-week-old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. SHR rats are hypertensive and hyperactive and have been proposed as a model of hyperactivity disorders. WKY rats are normotensive and hypoactive, and have been proposed as a model of depression. SHR rats had significantly greater orexin A-IR in the lateral, posterior, ventromedial and anterior hypothalamic regions, and in the olfactory tubercles, septum, thalamus, amygdala, striatum, cortex, colliculi, midbrain, pons and medulla. We also studied immunoreactivity for melaninconcentrating hormone and for cocaine and amphetamine-regulated transcript peptide in hypothalamic regions of these animals; unlike orexin A-IR, no significant difference was noted between the two strains. The difference in orexin A-IR between these two inbred strains suggests that orexin A may be involved in the difference in their activity patterns. The differences in orexin A-IR between SHR and WKY strains requires further investigation to distinguish the role of orexins in activity and blood pressure regulation.
OREXINS INCREASE ACTIVE BEHAVIOUR AND CNS OREXIN A IMMUNOREACTIVITY IS SIGNIFICANTLY DIFFERENT BETWEEN SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS Taheri, Shahrad; Sunter, David; Hafizi, Sepehr; Dakin, Catherine; Murphy, Kevin; Ghatei, Mohammad; Bloom, Stephen Imperial College School of Medicine, London, United Kingdom Orexins (A and B), neuropeptides synthesised in the dorsolateral hypothalamus, have been implicated in the regulation of arousal and the sleep/wake cycle. We administered orexins into the third ventricle of Wistar rats in the early light phase and observed animal behaviour over the next 24 hours, In the first 4 hours postinjection, orexins significantly increased active behaviour such as locomotion, grooming and burrowing. In the subsequent 20 hours, orexin A resulted in reduced activity and increased still behaviour, suggesting a disruption in the circadian pattern of activity. Using a sensitive and specific radioimmunoassay for orexin A, we studied orexin A immunoreactivity (orexin A-IR) in discrete CNS regions of 12-week-old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. SHR rats are hypertensive and hyperactive and have been proposed as a model of hyperactivity disorders. WKY rats are normotensive and hypoactive, and have been proposed as a model of depression. SHR rats had significantly greater orexin A-IR in the lateral, posterior, ventromedial and anterior hypothalamic regions, and in the olfactory tubercles, septum, thalamus, amygdala, striatum, cortex, colliculi, midbrain, pons and medulla. We also studied immunoreactivity for melaninconcentrating hormone and for cocaine and amphetamine-regulated transcript peptide in hypothalamic regions of these animals; unlike orexin A-IR, no significant difference was noted between the two strains. The difference in orexin A-IR between these two inbred strains suggests that orexin A may be involved in the difference in their activity patterns. The differences in orexin A-IR between SHR and WKY strains requires further investigation to distinguish the role of orexins in activity and blood pressure regulation.