Response of the guinea-pig urinary bladder to purine and pyrimidine nucleotides

The ability of purines and pyrimidines to cause and inhibit contractile responses was examined in strips of guinea-pig urinary bladder. Adenosine 5'-triphosphate (ATP), beta, gamma-methylene ATP (APPCP), adenosine 5'-diphosphate (ADP), guanosine 5'-triphosphate (GTP) and cytidine 5'-triphosphate (CTP) caused concentration-dependent contractions of the bladder. The order of potency was APPCP greater than ATP greater than GTP=CTP greater than ADP. Adenosine 5'-monophosphate, adenosine, guanosine 5'-diphosphate, guanosine 5'-monophosphate, guanosine, cytidine 5'-diphosphate, cytidine 5'-monophosphate, adenosine, guanosine 5'-diphosphate, guanosine 5'-monophosphate, guanosine, cytidine 5'-diphosphate, cytidine 5'-monophosphate and cytidine had no apparent contractile activity up to 10(-3) M. Cumulative administrations of 5 X 10(-4) M APPCP, ATP, ADP, GTP or CTP resulted in complex desensitization of the tissue to the contractile activity of the nucleotide. Tissues desensitized to GTP or CTP were non-responsive to ATP suggesting cross-tachyphylaxis. Nucleotides lacking contractile activity or nucleosides did not alter the response of the bladder to ATP; except AMP and adenosine which significantly reduced the contraction. These results suggest that the polyphosphate structure, and not the base, is the determining portion of the nucleotide for promoting contractile activity and the development of tachyphylaxis.