title: Nociceptin receptor signaling in sympathetic neurons from septic rats.
abstract: BACKGROUND
  The endogenous opioid peptide, nociception (Noc), contributes to the regulation of systemic blood pressure and regional blood flow. Recent clinical and animal studies have reported that Noc and its receptor (nociceptin/orphanin FQ [NOP]) are involved in inflammation and sepsis. The purpose of the present study was to examine the modulation of Ca(2+) channels by Noc in acutely isolated stellate ganglion (SG) neurons from control and septic rats.
  
  
  METHODS
  Sepsis was induced in male Sprague-Dawley rats via cecal ligation and puncture. SG neurons were isolated 24 and 72 h after sepsis induction. Thereafter, the concentration-response relationships for the Noc-stimulated NOP receptor Ca(2+) current inhibition were determined using the whole-cell patch clamp technique. In addition, the Noc precursor (prepronociceptin [PNOC]) and NOP receptor messenger RNA (mRNA) levels were determined by quantitative real-time polymerase chain reaction, and PNOC protein levels were measured by Western blot analysis.
  
  
  RESULTS
  Comparison of the Noc concentration-response relationships in SG neurons from control and septic rats 24 h after sepsis revealed similar potency and efficacy. Moreover, 72 h after sepsis, neurons from control and septic rats exhibited an increased potency compared with both groups at the 24-h time point--an effect that was more pronounced in neurons from septic rats. PNOC mRNA levels were significantly greater in SG neurons isolated from septic rats compared with control neurons, but NOP receptor mRNA levels remained unchanged during the 72-h period.
  
  
  CONCLUSIONS
  Our study demonstrates the cecal ligation and puncture model-induced temporal upregulation of components within the NOP receptor signaling pathway in rat sympathetic neurons. As SG neurons provide the main sympathetic input to the heart, an increased Noc release and potency during sepsis may compromise cardiovascular function.
authors.affiliation: Department of Surgery, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Lacee J
authors.initials: LJ
authors.lastname: Laufenberg
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Weller
authors.forename: Charles H
authors.initials: CH
authors.lastname: Lang
authors.forename: Victor
authors.initials: V
authors.lastname: Ruiz-Velasco
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D002432:Cecum / Q000293:injuries; D004195:Disease Models, Animal; D008026:Ligation; D008297:Male; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018847:Opioid Peptides / Q000502:physiology; D018408:Patch-Clamp Techniques; D011498:Protein Precursors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000502:physiology*; D018805:Sepsis / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*; D013233:Stellate Ganglion / Q000166:cytology / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D015220:Calcium Channels; D018847:Opioid Peptides; D011498:Protein Precursors; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C121527:prepronociceptin; C000722285:Oprl1 protein, rat
keywords: Ca(2+) channels; NOP receptor; Nociceptin; Prepronociceptin; Sepsis; Stellate ganglion