Abstract

During exercise or dry air-induced asthma, airway walls cool. However, the role of temperature in the regulation of airway tone is not clear. Protein kinase C (PKC) is an important second messenger in the mediation of cell responses. To explore whether changes in temperature affect pathways involving PKC in airways, we examined the effects of phorbol esters, potent activators of PKC, in guinea pig tracheal rings at various temperatures. Phorbol-12,13-diacetate (PDA) caused a reduction in tracheal tone at 37 degrees C and an increase in tone when temperature was reduced to 22 degrees C. Increases in tone were also produced by PDA when cell membranes were depolarized by ouabain (10 microM) or KCl (30 mM) at 37 degrees C. Contractions produced by PDA at 22 degrees C were inhibited by lipoxygenase inhibitors [ETYA (5,8,11,14-eicosatetraynoic acid), NDGA (nordihydroguaiaretic acid) and phenidone] and a leukotriene receptor antagonist [FPL 55712 (sodium 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxyl] -4-oxo-8-propyl-4H-1-benzopyran-2-carboxylate)]. Contractions produced by PDA at 37 degrees C or 22 degrees C in the presence of ouabain (10 mM) or KCl (30 mM) were not affected by these drugs. These results indicate that changes in temperature have profound effects on responses resulting from PKC activation. At low temperature, the lipoxygenase pathway mediates responses. Thus, cooling has the potential to modify a major intracellular pathway regulating physiological responses of the airways.