Prostaglandin E-2 activates the ciliary beat frequency of cultured human nasal mucosa via the second messenger cyclic adenosine monophosphate

Prostaglandins influence the ciliary beat frequency (CBF) of ciliated nasal epithelial cells and a stimulatory effect has been described for prostagla ndin E-2? (PGE(2)). Until now, it is not known whether PGE(2) has direct ci liostimulatory properties or acts through a second messenger. In this study we investigated whether cyclic adenosine monophosphate (cAMP) is implicate d in the signal transduction pathway of PGE(2)-induced activation of CBF. C iliated cells of the nasal mucosa were cultured for up to 5 days whereafter the culture medium was removed and the cells were incubated with different concentrations of test solutions. The ciliated cells were recorded under a phase-contrast microscope and viewed in slow motion to count the frequency . PGE(2) led to a dose-dependent increase in CBF. This became significant a t concentrations of 10(-10) and 10(-5) M (P < 0.01) but not at 10(-13) M (P > 0.05). Addition of cAMP (10(-10) to 10(-5) M) caused a significant (P < 0.01) increase in CBF, whereas depletion of endogenous cAMP after pre-incub ation with the adenylate cyclase activator forskolin (10(-5) M) prevented t he PGE(2)-induced increase in CBF (P > 0.05). The ciliostimulatory effect o f PGE(2) depends on an intact functioning of adenylate cyclase. These resul ts point out that cAMP is directly implicated in the signal transduction pa thway of PGE(2)-induced stimulation of CBF in cultured human ciliated cells of the nasal mucosa.