ATP transients accompany spontaneous contractions in isolated guinea‐pig detrusor smooth muscle

Abstract

Spontaneous contractions are characteristic of the bladder wall, but their origins remain unclear.Activity is reduced if the mucosa is removed but does not disappear, suggesting that a fraction arises from the detrusor. We tested the hypothesis that spontaneous detrusor contractions arise from spontaneous ATP release. Guinea-pig detrusor strips, without mucosa, were superfused with Tyrode solution at 36 • C. Preparations were subjected to electrical field stimulation (EFS; 3 s trains at 90 s intervals) to produce nerve-mediated contractions, abolished by 1 µM TTX. Amperometric ATP electrodes on the preparation surface recorded any ATP released. Spontaneous contractions and ATP transients were recorded between EFS trains. Nerve-mediated contractions were attenuated by atropine and , -methylene ATP; in combination, they nearly abolished contractions, as did nifedipine. Contractions were accompanied by ATP transients that were unaffected by atropine but inhibited by TTX and greatly attenuated by nifedipine. Spontaneous contractions were accompanied by ATP transients, with a close correlation between the magnitudes of both transients. ATP and contractile transients persisted with TTX, atropine and nifedipine.Immediately after a nerve-mediated contraction and ATP transient, there was a longer interval than normal before spontaneous activity resumed. Spontaneous contractions and ATP transients are proposed to arise from ATP leakage from nerve terminals innervating the detrusor.Extracellular ATP has a greater functional significance in humans who suffer from detrusor overactivity (spontaneous bladder contractions associated with incontinence) owing to its reduced hydrolysis at the nerve-muscle interface. This study shows the origin of spontaneous activity that might be exploited to develop a therapeutic management of this condition. K E Y W O R D SATP, detrusor smooth muscle, spontaneous contractions

Selective reduction of neurotransmitter release by cAMP-dependent pathways in mouse detrusor

“…Adenosine may also exert actions at other sites in the urinary bladder and contribute to its overall effects. Spontaneous contractions in isolated detrusor smooth muscle are accompanied by similar ATP release transients from motor nerves (36) and may represent leakage from the two vesicular pools measured in this study. However, A 1 receptor involvement was not supported by the fact that neither adenosine nor CPA altered spontaneous contractions or accompanying EJPs (31).…”

Inhibition of Female and Male Human Detrusor Smooth Muscle Contraction by the Rac Inhibitors EHT1864 and NSC23766

“…At least partially, the limited efficacy of anticholinergics may be explained by noncholinergic detrusor contractions. Spontaneous contractions, which occur in OAB, are supposed to be caused by adenosine triphosphate (ATP) (Akino et al, 2008;Kushida and Fry, 2016;McCarthy et al, 2019). In addition, different prostanoids occur or are even produced within the bladder, which may induce detrusor contraction independently from other mediators or in concert with them (Collins et al, 2009;Rahnama'i et al, 2012).…”

Bladder attack: transient bladder ischemia leads to a reversible decrease in detrusor compliance

“…While one may speculate on the mechanism behind the increased detrusor tone with ischemia based on the observed blocking effect of atropine, molecular studies are needed to further evaluate and confirm the findings. Measurements of acetylcholine and adenosine triphosphate (ATP) levels in future studies may be warranted given the established relationship demonstrated in other similar animal models (21,22). The scope of the data is also limited by the relatively low number of bladder and detrusor specimens, but the consistency of the results provides reassurance that findings are valid.…”