Direct effects of adenosine and adenine nucleotides on isolated human urinary bladder and their influence on electrically induced contractions

Adenosine triphosphate concentration-dependent contracted strips of isolated human urinary bladder. Three types of responses were recognized. One consisted of an initial, transient, phasic contraction followed by a sustained tonic response, another lacked the tonic part and the 3rd had intermediate-type characteristics. Adenosine diphosphate produced an intermediate type of contraction, while adenosine monophosphate, adenosine and 2-chloroadenosine had no effect. Preparations obtained from hypertrophic bladders were more sensitive to adenosine triphosphate than macroscopically normal preparations. Indomethacin abolished tonic responses and reduced phasic adenosine triphosphate and adenosine diphosphate induced responses by about 30 per cent; addition of PGE2 and PGF2 alpha reestablished the phasic responses. Atropine, physostigmine, hexamethonium and phentolamine had no effect on the adenosine triphosphate induced contractions. These contractions were reduced by 33 to 48 per cent after nifedipine pretreatment and abolished within 10 minutes in a calcium-free medium. The response to transmural nerve stimulation was initially stimulated and then reduced by 30 to 80 per cent by purines in the order of potency ATP greater than APPCP = ADP greater than AMP greater than adenosine = 2-chloroadenosine. Acetylcholine induced contractions were reduced by 10 to 30 per cent. Indomethacin inhibited the response to transmural nerve stimulation by about 30 per cent but did not influence inhibition produced by adenosine triphosphate. Atropine-resistant responses to transmural nerve stimulation were significantly reduced by both adenosine triphosphate and indomethacin; nifedipine abolished the responses. The results suggest that adenosine triphosphate has a calcium-dependent direct contractive effect on isolated human urinary bladder and also that it may release prostaglandins. Muscular hypertrophy seems to increase the sensitivity to adenosine triphosphate. The response to transmural nerve stimulation was influenced by adenosine triphosphate probably both by prejunctional and postjunctional effects.