title: Activation of opioid μ-receptors in the commissural subdivision of the nucleus tractus solitarius abolishes the ventilatory response to hypoxia in anesthetized rats.
abstract: BACKGROUND
  : The commissural subnucleus of the nucleus tractus solitarius (comNTS) is a key region in the brainstem responsible for the hypoxic ventilatory response (HVR) because it contains the input terminals of the carotid chemoreceptor. Because opioids inhibit the HVR via activating central μ-receptors that are expressed abundantly in the comNTS, the authors of the current study asked whether activating local μ-receptors attenuated the carotid body-mediated HVR.
  
  
  METHODS
  : To primarily stimulate the carotid body, brief hypoxia (100% N2) and hypercapnia (15% CO2) for 10 s and/or intracarotid injection of NaCN (10 μg/100 μl) were performed in anesthetized and spontaneously breathing rats. These stimulations were repeated after: (1) microinjecting three doses of μ-receptor agonist [d-Ala2, N-Me-Phe4, Gly-ol]-Enkephalin (DAMGO) (approximately 3.5 nl) into the comNTS; (2) carotid body denervation; and (3) systemic administration of DAMGO (300 μg/kg) without and with previous intracomNTS injection of d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2, a μ-receptor antagonist.
  
  
  RESULTS
  : Study results showed that DAMGO at 0.25 and 2.5, but not 0.025 mM, caused a similar decrease in baseline ventilation (approximately 12%). DAMGO at 0.25 mM largely reduced (64%) the HVR, whereas DAMGO at 2.5 mM abolished the HVR (and the VE response to NaCN) and moderately attenuated (31%) the hypercapnic ventilatory response. Interestingly, similar HVR abolition and depression of the hypercapnic ventilatory response were observed after carotid body denervation. Blocking comNTS μ-receptors by d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 significantly attenuated the HVR depression by systemic DAMGO with little change in the DAMGO modulatory effects on baseline ventilation and the hypercapnic ventilatory response.
  
  
  CONCLUSIONS
  : The data suggest that opioids within the comNTS, via acting on μ-receptors, are able to abolish the HVR by affecting the afferent pathway of the carotid chemoreceptor.
authors.affiliation: Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
authors.forename: Zhenxiong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhuang
authors.forename: Cancan
authors.initials: C
authors.lastname: Zhang
authors.forename: Fadi
authors.initials: F
authors.lastname: Xu
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002344:Carotid Body / Q000502:physiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000502:physiology*; D012119:Respiration / Q000187:drug effects; D017552:Solitary Nucleus / Q000502:physiology*
chemical_list: D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-