A new bioassay to study contractile and relaxant effects of PGE2 on perfused guinea pig trachea.
The aim of this study was to investigate the effects of PGE2 under different experimental conditions. By a newly developed imaging bioassay system, changes of the diameter of isolated perfused guinea-pig tracheal tubes were continuously measured. The results were compared with those of a conventional ring bioassay system. The effect of PGE2 was examined in epithelium-intact and-denuded tubes. The potency of PGE2 applied to the inner surface of tube preparations was significantly enhanced by about six-fold in epithelium-denuded compared with epithelium-intact tubes. In rings there was no difference. The results suggest a potential role of epithelium in assessment of airway reactivity in vivo. The study demonstrates, that the effects of PGE2 depend critically on the experimental approach. PGE2 (0.01 nmol 1(-1)-1 mumol 1(-1)) contracted tracheal tubes, but resulted in relaxation of ring preparations under basal tone. The spontaneous tone of guinea pig trachea can be reduced with the cyclooxygenase inhibitor diclofenac. Pretreatment of the rings with diclofenac reversed the relaxation into contraction. Preincubation of tube preparations with diclofenac had no effect on basal tone, indicating that there was no inherent spontaneous prostanoid-dependent tone or the mediators may be washed out at a relatively fast rate and, therefore, tone may not be apparent.
Baersch
G
G
Department of Clinical Pharmacology, Hannover Medical School, Germany.
Frölich
J C
JC
D000704:Analysis of Variance; D000818:Animals; D001681:Biological Assay; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D004008:Diclofenac / Q000633:toxicity*; D015232:Dinoprostone / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010120:Oxytocics / Q000494:pharmacology*; D015203:Reproducibility of Results; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D010120:Oxytocics; D004008:Diclofenac; D015232:Dinoprostone