Peripheral opioidergic regulation of the tracheobronchial mucociliary transport system.
We hypothesized that, in the airway mucosa, opioids are inhibitory neural modulators that cause an increase in net water absorption in the airway mucosa (as in the gut). Changes in bidirectional water fluxes across ovine tracheal mucosa in response to basolateral application of the opioid peptides beta-endorphin, dynorphin A-(1-8), and [d-Ala(2), d-Leu(5)]-enkephalin (DADLE) were measured. beta-Endorphin and dynorphin A-(1-8) decreased luminal-to-basolateral water fluxes, and dynorphin A-(1-8) and DADLE increased basolateral-to-luminal water flux. These responses were electroneutral. In seven beagle dogs, administration of aerosolized beta-endorphin (1 mg) to the tracheobronchial airways decreased the clearance of radiotagged particles from the bronchi in 1 h from 34.7 to 22.0% (P < 0.001). Naloxone abrogated the beta-endorphin-induced changes in vitro and in vivo. Contrary to our hypothesis, the opioid-induced changes in water fluxes would all lead to a predictable increase in airway surface fluid. The beta-endorphin-induced increases in airway fluid together with reduced bronchial mucociliary clearance may produce procongestive responses when opioids are administered as antitussives.
Wang
Lian
L
Departments of Medicine and Bioengineering University of Illinois at Chicago, and Veterans Affairs Health Care System, West Side, Chicago, Illinois 60612, USA.
Tiniakov
Ruslan L
RL
Yeates
Donovan B
DB
D000336:Aerosols; D000818:Animals; D001980:Bronchi / Q000502:physiology*; D004285:Dogs; D004357:Drug Synergism; D004399:Dynorphins / Q000494:pharmacology*; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007273:Injections, Intramuscular; D007477:Ions; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects*; D009270:Naloxone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000008:administration & dosage; D010446:Peptide Fragments / Q000494:pharmacology*; D012756:Sheep; D014132:Trachea / Q000378:metabolism / Q000502:physiology*; D014867:Water / Q000378:metabolism; D001615:beta-Endorphin / Q000008:administration & dosage / Q000494:pharmacology*
D000336:Aerosols; D007477:Ions; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D014867:Water; D009270:Naloxone; D001615:beta-Endorphin; D016308:Enkephalin, Leucine-2-Alanine; D004399:Dynorphins; C026770:dynorphin (1-8)