Relaxation of guinea‐pig tracheal smooth muscle to arachidonate is converted to contraction following epithelium removal

Abstract

The effect of epithelium removal on responses of guinea‐pig isolated trachealis to sodium arachidonate has been examined. Arachidonate (100 μm) caused relaxation of epithelium‐intact preparations, but following epithelium removal, the response to arachidonate was converted to contraction. In the presence of indomethacin (1 μm), arachidonate caused contraction in intact and denuded trachea. Arachidonate also produced concentration‐dependent effects, the qualitative nature of which varied with the presence or absence of the epithelium. In the presence of indomethacin, tracheal strips contracted in a concentration‐dependent manner whether or not the epithelium had been removed. Nordihydroguaiaretic acid (NDGA; 11 μm) markedly inhibited the contractile response of denuded strips to arachidonate. In intact tissues this lipoxygenase inhibitor converted the arachidonate‐induced relaxation to a concentration‐dependent contraction. The contraction to arachidonate, in the presence of NDGA, was epithelium‐dependent. In the presence of both indomethacin and NDGA, responses to arachidonate were abolished. It is concluded that the relaxation of guinea‐pig trachea to arachidonic acid is epithelium‐dependent and is mediated by an inhibitory product of the cyclo‐oxygenase metabolic pathway. The contraction in denuded trachea, and trachea in the presence of indomethacin, may be mediated by lipoxygenase products of arachidonic acid metabolism, i.e. peptidoleukotrienes. The mediator of the epithelium‐dependent contraction in NDGA‐treated tissues is unknown.

Evidence that the histamine sensitivity and responsiveness of guinea‐pig isolated trachea are modulated by epithelial prostaglandin E2 production

“…We observed (this study) that the contraction of rubbed preparations with AA (10pM) was attenuated by treatment of these tissues with indomethacin. Previous investigators (Nijkamp & Folkerts, 1987;Farmer et al, 1987) were unable to prevent the AA contractile effect in rubbed preparations with indomethacin. The discrepancy between these observations and the results presented here may be due to the high concentrations of AA (100pM) used in those initial studies.…”

Popcorn Flavoring Effects on Reactivity of Rat Airways in Vivo and in Vitro

“…In the presence of the epithelium, the concentration-response curve obtained after adding MCh mucosally was shifted rightward of the EL curve and was characterized by a smaller maximum response ( Figure 5 and Table 2). The lesser reactivity to MCh after IL addition in intact trachea is a reflection of the epithelial diffusion barrier as well as the release of epithelial-derived modulatory factors (Farmer et al, , 1987Fedan et al, 2006;Fedan and Frazer, 1992;Smith et al, 1993).…”

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

“…Several investigators have reported alterations in relaxation in ASM from animal models of asthma [322][323][324][325]. Unfortunately, most of them dealt with isometric relaxation (relaxation of tension in muscle maintained at a constant length after cessation of stimulation), which provided information relating to stiffening of the airway wall and not to the relevant parameter of airway lumen narrowing [322][323][324]. In vivo measurements of FEV1 and specific Gaw are better in this regard, but suffer from the drawback that multiple confounding variables are operating simultaneously.…”