Effect of carbachol and norepinephrine on phosphatidyl inositol hydrolysis and cyclic AMP levels in guinea pig urinary tract.

Muscarinic cholinergic and adrenergic agonist-induced changes in [3H]-phosphatidyl inositol (PI) hydrolysis and cyclic AMP (cAMP) levels were measured in guinea pig ureter, urethra and bladder dome. In the ureter, carbachol, norepinephrine and phenylephrine rapidly increased PI hydrolysis and basal cAMP levels, but did not decrease forskolin-stimulated cAMP levels. In the bladder dome, norepinephrine and phenylephrine produced a rapid but transitory increase in PI hydrolysis, but did not affect forskolin-stimulated cAMP levels. Carbachol produced a rapid and sustained increase in PI hydrolysis and also, at high concentrations, decreased forskolin-stimulated cAMP levels. In the urethra, norepinephrine and carbachol rapidly decreased forskolin-stimulated cAMP levels and later increased PI hydrolysis. Our data suggest that the predominant second messenger system in the ureter, dome, or urethra is more dependent on the tissue than on the agonist. These tissue-specific, agonist-induced rapid changes in second messenger levels may help coordinate the contraction-relaxation phenomena necessary for urinary tract function.