Direct Effects of Adenosine and Adenine Nucleotides on Isolated Human Urinary Bladder and their Influence on Electrically Induced Contractions

Abstract

ATP concentration-dependently contracted strips of isolated human urinary bladder. Three types of responses were recognized. One consisted of an intial, transient, phasic contraction followed by a sustained tonic response, another lacked the tonic part and the 3rd had intermediate-type characteristics. ADP produced an intermediate type of contraction, while AMP, adenosine and 2-chloroadenosine had no effect. Preparations obtained from hypertrophic bladders were more sensitive to ATP than macroscopically normal preparations. Indomethacin abolished tonic responses and reduced phasic ATP and ADP induced responses by about 30%; addition of PG[prostaglandin]E2 and PGF2.alpha. reestablished the phasic responses. Atropine, physostigmine, hexamethonium and phentolamine had no effect on the ATP induced contractions. These contractions were reduced by 33-48% after nifedipine pretreatment and abolished within 10 min in a Ca2+-free medium. The response to transmural nerve stimulation was initially stimulated and then reduced by 30-80% by purines in the order of potency ADP > APPCP = ADP > AMP > adenosine = 2-chloroadenosine. Acetylcholine induced contractions were reduced by 10-30%. Indomethacin inhibited the response to transmural nerve stimulation by about 30% but did not influence inhibition produced by ATP. Atropine-resistant responses to transmural nerve stimulation were significantly reduced by both ATP and indomethacin; nifedipine abolished the responses. Evidently ATP has a Ca2+-dependent direct contractive effect on isolated human urinary bladder and also that it may release PG. Muscular hypertrophy seems to increase the sensitivity to ATP. The response to transmural nerve stimulation was influenced by ATP probably both by prejunctional and postjunctional effects.