Prostaglandins influence the ciliary beat frequency (CBF) of ciliated nasal epithelial cells and a stimulatory effect has been described for prostaglandin E2 (PGE2). Until now, it is not known whether PGE2 has direct ciliostimulatory properties or acts through a second messenger. In this study we investigated whether cyclic adenosine monophosphate (cAMP) is implicated in the signal transduction pathway of PGE2-induced activation of CBF. Ciliated 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. PGE2 led to a dose-dependent increase in CBF. This became significant at 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-incubation with the adenylate cyclase activator forskolin (10(-5) M) prevented the PGE2-induced increase in CBF (P > 0.05). The ciliostimulatory effect of PGE2 depends on an intact functioning of adenylate cyclase. These results point out that cAMP is directly implicated in the signal transduction pathway of PGE2-induced stimulation of CBF in cultured human ciliated cells of the nasal mucosa.