Prostaglandins differentially modulate eupnea, sigh and gasping activity

The inducible enzyme Cyclooxygenase‐2 (COX‐2) is expressed at basal levels in the brain. A number of stimuli including hypoxia increase COX‐2 expression (Yamagata et al.1993). Prostaglandins, the major reaction products of this pathway have been identified as modulators of neuronal respiratory activity (Hoffstetter et al. 2007). To further characterize the effects of prostaglandins, especially PGE2, we used extra‐ and intracellular recordings from the preBötzinger Complex, the presumed site for inspiratory rhythm generation, and in vivo recordings from freely breathing animals. These recordings revealed that bath applied PGE2 had differential effects on the frequency of “fictive sighs”, “fictive eupnea” and “fictive gasping”. At low concentrations PGE2 application increased the sigh burst frequency, while eupneic burst activity was not significantly altered. In contrast, higher concentrations of PGE2 caused an increase in eupneic burst frequency. Moreover, low and high concentrations of PGE2 increased the amplitude of gasp bursts. PGE2 directly injected into the preBötzinger Complex had similar effects on sigh and eupneic frequency in freely breathing animals. Thus, our results suggest that prostaglandins are important modulators of respiration and exhibit differential concentration‐dependent effects. These dose‐dependent effects might correspond to basal and stimulated levels of PGE2.