Epithelium-dependent potentiation of anaphylactic contractions by beta-endorphin in tracheae isolated from actively sensitized guinea-pigs.
1. It has been shown that opioid peptides modulate airway function. In the present study, the effect of beta-endorphin on antigen-induced contractions of isolated tracheal rings from actively sensitized guinea-pigs has been studied. 2. beta-Endorphin had a concentration-dependent bimodal effect on anaphylactic contractions of the trachea. Low concentrations of beta-endorphin (10(-10) and 10(-8) M) significantly potentiated anaphylactic contractions, whereas higher concentrations (10(-7) and 10(-6) M) significantly suppressed anaphylactic contractions of guinea-pig trachea. 3. beta-Endorphin in concentrations of 10(-8) M and 10(-7) M did not affect the responsiveness of the tracheal rings to histamine or leukotriene D4. This indicates that beta-endorphin does not influence the responsiveness of tracheal smooth muscle to anaphylactic mediators. 4. In the presence of the non-selective opioid receptor antagonist naloxone, 10(-8) M beta-endorphin still potentiated the anaphylactic contractions of the trachea. In addition, an equimolar concentration of des-Tyr1-beta-endorphin, a fragment of beta-endorphin without opioid-like activity, also potentiated anaphylactic contractions. The potentiation of anaphylactic contraction by 10(-8) M beta-endorphin is not therefore mediated by classical opioid-receptors. 5. In the presence of naloxone, 10(-7) M, beta-endorphin did not suppress anaphylactic contractions of the trachea. Thus, the suppression of anaphylactic contraction is mediated via a classical opioid-receptor. 6. In epithelium-denuded trachea, both 10(-8) and 10(-7) M beta-endorphin suppressed the anaphylactic contractions, whereas 10(-8) and 10(-7) M des-Tyr1-beta-endorphin did not affect anaphylactic contractions. It is concluded that the potentiation of the anaphylactic contraction in intact trachea is epithelium-dependent whereas the suppression of the anaphylactic contraction is epithelium-independent.
Van Oosterhout
A J
AJ
Department of Pharmacology, Faculty of Pharmacy, University of Utrecht, The Netherlands.
Celeda
L
L
Delsman
K C
KC
de Wied
D
D
Nijkamp
F P
FP
D000707:Anaphylaxis / Q000276:immunology / Q000503:physiopathology*; D000818:Animals; D004848:Epithelium / Q000502:physiology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000494:pharmacology; D013189:SRS-A / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D001615:beta-Endorphin / Q000494:pharmacology*
D010446:Peptide Fragments; D013189:SRS-A; D009270:Naloxone; D001615:beta-Endorphin; D006632:Histamine; D010047:Ovalbumin