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Differential effects of epithelium removal on the responsiveness of guinea‐pig tracheal smooth muscle to bronchoconstrictors
Author(s) -
Hay D.W.P.,
Farmer S.G.,
Raeburn D.,
Muccitelli R.M.,
Wilson K.A.,
Fedan J.S.
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb11334.x
Subject(s) - epithelium , leukotriene d4 , respiratory epithelium , guinea pig , medicine , endocrinology , biology , leukotriene , thromboxane , transepithelial potential difference , prostanoid , chemistry , prostaglandin , ion transporter , biochemistry , platelet , genetics , membrane , asthma
1 The influence of the epithelium on contractions produced by the peptidoleukotrienes, 5‐hydroxytryptamine (5‐HT) and the thromboxane mimetic, U‐44069, was examined in trachea from control and ovalbumin‐sensitized guinea‐pigs. 2 In control tissues removal of the epithelium produced an approximately 2 to 4 fold leftward shift in leukotriene C 4 (LTC 4 ) and LTD 4 concentration‐response curves, but no effect on LTE 4 ‐induced contractions. Similar results were obtained in preparations from ovalbumin‐sensitized animals. 3 Responses produced by 5‐HT or U‐44069 were similar in the presence and absence of the epithelium in control guinea‐pigs. 4 Indomethacin produced contrasting effects on leukotriene‐induced contractions in control guinea‐pigs: an increase in sensitivity to LTC 4 in the presence but not absence of the epithelium, no effect on LTD 4 ‐induced contractions and a decrease in sensitivity to LTE 4 in both epithelium‐containing and epithelium‐free preparations. 5 These results indicate that there is selectivity in the effects of epithelium removal on agonist‐induced contractions of the guinea‐pig trachea. This provides further evidence for the modulatory influence of the epithelium on the reactivity of mammalian airway smooth muscle and supports the postulated existence of an epithelium‐derived inhibitory factor. The observation that in intact trachea indomethacin mimics the effects of epithelium removal on LTC 4 ‐induced responses, suggests the involvement of a prostanoid(s) in this phenomenon.