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Molecular Pharmacology, Vol 19, 525-528, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics
1 Division of Urology, Department of Surgery, University of Pennsylvania School of Medicine and the Veterans Administration
Medical Center, Philadelphia, Pennsylvania 19104
There is circumstantial evidence that ATP may be an excitatory neurohumoral transmitter in the urinary bladder of several species. Muscle bath studies in vitro demonstrated
that exogenously applied ATP can produce a dose-dependent contraction of the rabbit
urinary bladder. These studies indicate that the concentrations of ATP necessary to
stimulate bladder contraction are significantly greater than one would expect if ATP were
acting through a neurohumoral receptor system. The purpose of our study was to compare
the contractile action of ATP on isolated strips of urinary bladder with the ATP hydrolysis
activity of these strips. The results from these studies demonstrate that, over the time
course of the contractile effect of ATP, less than 0.1% of the ATP present in the bath is
hydrolyzed by the tissue. Thus, the requirement for high concentrations of ATP for
contractile stimulation cannot be ascribed to ATP hydrolysis by the tissue. Additionally,
it is interesting to note that
,
-methylene ATP was approximately 100 times as potent
as disodium ATP in its ability to stimulate contraction in the rabbit urinary tract. This
difference in potency is probably a function of the structure of
,
-methylene ATP rather
than its resistance to hydrolysis by ATPase.