Activation of opioid μ-receptors, but not δ- or κ-receptors, switches pulmonary C-fiber-mediated rapid shallow breathing into an apnea in anesthetized rats

Respir Physiol Neurobiol. 2012 Sep 30;183(3):211-7. doi: 10.1016/j.resp.2012.06.032. Epub 2012 Jul 11.


Rapid shallow breathing (RSB) is mainly mediated by bronchopulmonary C-fibers (PCFs). We asked whether this RSB could be modulated by opioids. In anesthetized rats right atrial bolus injection of phenylbiguanide (PBG) to evoke RSB was repeated after: (1) intravenously giving fentanyl (μ-receptor agonist), DPDPE (δ-receptor agonist), or U-50488H (κ-receptor agonist); (2) fentanyl (iv) following naloxone methiodide, a peripheral opioid receptor antagonist; (3) bilateral microinjection of fentanyl into the nodose ganglia; (4) fentanyl (iv) with pre-blocking histamine H(1) and H(2) receptors by diphenhydramine and ranitidine. Systemic fentanyl challenge, but not DPDPE or U-50488H, switched the PBG-induced RSB to a long lasting apnea. This switch was blocked by naloxone methiodide rather than diphenhydramine and ranitidine. After microinjecting fentanyl into the nodose ganglia, PBG also produced an apnea. Our results suggest that activating μ-receptors is capable of turning the PCF-mediated RSB into an apnea, at least partly, via facilitating PCFs' activity and this switching effect appears independent of the released histamine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia / methods
  • Animals
  • Apnea / metabolism*
  • Apnea / physiopathology
  • Male
  • Nerve Fibers, Unmyelinated / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, delta / metabolism*
  • Receptors, Opioid, kappa / metabolism*
  • Receptors, Opioid, mu / metabolism*
  • Respiratory Mechanics / physiology*


  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu