THE ROLE OF CYCLIC-NUCLEOTIDES IN GUINEA-PIG BLADDER CONTRACTILITY

1 The effects of phosphodiesterase (PDE) inhibition and forskolin pret reatment on the contractile responses of guinea-pig urinary bladder st rips to electrical field stimulation, carbachol, ATP and KCl were stud ied. 2 Inhibition of cyclic AMP-specific PDE4 isozymes by rolipram sig nificantly reduced the contractile response of bladder strips to held stimulation. Rolipram also suppressed the contractile response to low concentrations of carbachol, but potentiated the response to high conc entrations. The contractile response to ATP was significantly reduced by rolipram treatment, but that to KCl was unaltered. 3 Inhibition of cyclic GMP-specific PDE5 isozymes by zaprinast had no effects on the c ontractile response of bladder strips to field stimulation, ATP or KCl . Zaprinast suppressed the contractile responses to 1 mu M carbachol a nd potentiated the response to high concentrations. 4 Contractile resp onses to field stimulation and to carbachol after pretreatment with th e adenylyl cyclase activator, forskolin, were qualitatively similar to those caused by rolipram treatment. beta-Adrenoceptor blockade with p ropranolol partially reversed the inhibitory effects of rolipram on th e response to field stimulation. 5 Rolipram significantly reduced the contractile response of bladder strips from sensitized guinea-pigs to ovalbumin challenge, but zaprinast was ineffective. PDE inhibition had similar effects on the responsiveness of control and of sensitized gu inea-pig bladder strips to field stimulation, carbachol, ATP and KCl. 6 The data suggest that the contractile response of guinea-pig bladder strips can be modified by increases in cyclic AMP levels.