Is the guinea pig trachea a good in vitro model of human large and central airways? Comparison on leukotriene-, methacholine-, histamine- and antigen-induced contractions.
To analyze comprehensively the relevance of the guinea pig trachea as a model of human large and central airways, the contractile effects of the peptidoleukotrienes (LTs), histamine, methacholine and antigen on guinea pig and human airways were compared in vitro. Although some differences were apparent, LTC4, LTD4, LTE4, histamine and methacholine had comparable EC50 values and elicited similar maximal responses in both guinea pig trachea and human bronchus (second-seventh generation). In the presence of l-serine borate (45 mM), LTC4 concentration-response curves were shifted significantly to the left in guinea pig trachea but not in human bronchus. Furthermore, the LT receptor antagonists (SK&F 102922 and FPL 55712) had similar potencies against LTC4- and LTD4-induced contractions of human bronchus, whereas, in the guinea pig trachea, they were much more effective antagonists of responses produced by LTD4 than those elicited by LTC4. These results provide further evidence that, unlike in human bronchus, LTC4- and LTD4-induced contractions in the guinea pig trachea are mediated via distinct leukotriene receptors. Ovalbumin-induced contractions of actively sensitized guinea pig tracheae exhibited the same profile as anti-immunoglobulin E-induced contractions of the passively sensitized human bronchus. Furthermore, antigen-induced contractions in both the guinea pig trachea and human bronchus possessed a similar sensitivity to inhibition by mepyramine (10 microM) and the LT antagonists (10 microM), added either alone or in combination. These results indicate that the isolated guinea pig trachea is a suitable model of human large and central airways.
Muccitelli
R M
RM
Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, Pennsylvania.
Tucker
S S
SS
Hay
D W
DW
Torphy
T J
TJ
Wasserman
M A
MA
D000328:Adult; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001881:Borates / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects; D002648:Child; D002867:Chromones / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology*; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin / Q000187:drug effects; D013189:SRS-A / Q000494:pharmacology*; D012694:Serine / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000276:immunology
D000941:Antigens; D001881:Borates; D002867:Chromones; D003998:Dicarboxylic Acids; D008688:Methacholine Compounds; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin; D013189:SRS-A; C040900:serine-borate complex; D016210:Methacholine Chloride; D012694:Serine; D006632:Histamine; C006312:FPL 55712; C046472:5-(2-(8-phenyloctyl)phenyl)-4,6-dithianonanedioic acid