Phosphoramidon augments contraction of guinea pig tracheal smooth muscle induced by histamine and leukotriene-D4.
Our previous studies have shown that the inhibition of neutral endopeptidase, an enzyme which degrades tachykinins, increases anaphylactic contraction of guinea pig tracheal smooth muscle. Anaphylactic release of tachykinin-like substances was indicated. To investigate this observation further, we examined the effects of phosphoramidon, an inhibitor of a neutral endopeptidase, on contraction induced by mediators of anaphylaxis. Phosphoramidon significantly increased histamine- and leukotriene D4-induced contractions of tracheal rings from unsensitized animals (by 14 and 48%, respectively), but failed to alter the contractile responses to prostaglandins D2 and F2 alpha. In tracheal rings preincubated with tachykinin antagonist-[D-Pro4, D-Trp7,9]-substance P(4-11), or in capsaicin-desensitized tracheal rings, phosphoramidon did not change histamine- and leukotriene D4-induced contractions. In the second part of the study, performed on tracheal rings obtained from ovalbumin-sensitized guinea pigs, we examined the effects of phosphoramidon on contractile responses to histamine and leukotrienes which are released after antigen challenge. The incubation of tracheal rings with H1-histamine receptor antagonist (diphenhydramine HCl) or leukotriene receptor antagonist (ICI 198.615) prevented a phosphoramidon-dependent increase of antigen-induced contraction. These results indicate that histamine and leukotrienes may be involved in the anaphylactic release of tachykinin-like substances or other neutral endopeptidase substratum.
Tudorić
N
N
Department of Anesthesiology, Zablocki Veterans Administration Medical Center, Milwaukee, Wisc.
Coon
R L
RL
Bosnjak
Z J
ZJ
D000707:Anaphylaxis / Q000139:chemically induced; D000818:Animals; D000941:Antigens / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D006020:Glycopeptides / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D017998:Leukotriene D4 / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D015230:Prostaglandin D2 / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors; D014132:Trachea / Q000502:physiology
D000941:Antigens; D006020:Glycopeptides; D007191:Indazoles; D013189:SRS-A; C054217:ICI 198615; D017998:Leukotriene D4; D006632:Histamine; D004155:Diphenhydramine; D015237:Dinoprost; D015260:Neprilysin; D015230:Prostaglandin D2; C008890:phosphoramidon