The role of cyclic nucleotides in guinea-pig bladder contractility.
1. The effects of phosphodiesterase (PDE) inhibition and forskolin pretreatment on the contractile responses of guinea-pig urinary bladder strips to electrical field stimulation, carbachol, ATP and KCl were studied. 2. Inhibition of cyclic AMP-specific PDE4 isozymes by rolipram significantly reduced the contractile response of bladder strips to field stimulation. Rolipram also suppressed the contractile response to low concentrations of carbachol, but potentiated the response to high concentrations. 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 contractile response of bladder strips to field stimulation, ATP or KCl. Zaprinast suppressed the contractile responses to 1 microM carbachol and potentiated the response to high concentrations. 4. Contractile responses to field stimulation and to carbachol after pretreatment with the adenylyl cyclase activator, forskolin, were qualitatively similar to those caused by rolipram treatment. beta-Adrenoceptor blockade with propranolol partially reversed the inhibitory effects of rolipram on the 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 guinea-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.
Longhurst
P A
PA
Division of Urology, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
Briscoe
J A
JA
Rosenberg
D J
DJ
Leggett
R E
RE
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D010047:Ovalbumin / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D020889:Rolipram; D001743:Urinary Bladder / Q000502:physiology*
D011688:Purinones; D011760:Pyrrolidinones; D005576:Colforsin; D002217:Carbachol; D010047:Ovalbumin; D000242:Cyclic AMP; C011145:zaprinast; D020889:Rolipram