title: Prostaglandin E2 activates the ciliary beat frequency of cultured human nasal mucosa via the second messenger cyclic adenosine monophosphate.
abstract: 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.
authors.affiliation: Department of Otorhinolaryngology Johannes-Gutenberg University Mainz, Germany.
authors.forename: B R
authors.initials: BR
authors.lastname: Haxel
authors.forename: D
authors.initials: D
authors.lastname: Schäfer
authors.forename: L
authors.initials: L
authors.lastname: Klimek
authors.forename: W J
authors.initials: WJ
authors.lastname: Mann
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects* / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects* / Q000503:physiopathology*; D015290:Second Messenger Systems / Q000187:drug effects* / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D005576:Colforsin; D000242:Cyclic AMP; D015232:Dinoprostone