Relationship between lower urinary tract symptoms and urinary ATP in patients with benign prostatic hyperplasia or overactive bladder

Abstract

We investigated whether the improvement of lower urinary tract symptoms (LUTS) and urinary adenosine triphosphate (ATP) level were related. Fifty-seven patients and 13 normal controls were enrolled in this study. All of the male patients had benign prostatic hyperplasia (BPH), and all of the female patients had overactive bladder (OAB). We administered an alpha-1 adrenergic receptor antagonist (tamsulosin hydrochloride) for BPH, while OAB patients received an anti-muscarinic agent (propiverine hydrochloride). Before and after treatment, we examined LUTS and urinary ATP/creatinine ratio. The urinary ATP/creatinine ratio was lower in males than females in both controls and patients. In the BPH patients, administration of the alpha-1 receptor antagonist decreased LUTS and urinary ATP/creatinine ratio, and improvement of LUTS was greater in patients with a high baseline urinary ATP level. In the OAB patients, administration of the anti-muscarinic agent decreased LUTS and urinary ATP/creatinine ratio, and improvement of LUTS was greater in patients with a high baseline urinary ATP level. Improvement of LUTS by treatment with the alpha-1 receptor antagonist or the anti-muscarinic agent was related to the decrease of urinary ATP/creatinine ratio in patients with BPH or OAB. Measurement of urinary ATP can be used as a marker of pathologic bladder function.Alpha-1 adrenergic receptor antagonists are the firstline medications for the treatment of benign prostatic hyperplasia (BPH), because these drugs relax the smooth muscle in the prostate and decrease resistance to urine flow in the prostatic urethra (6, 10). These antagonists improve both urinary voiding disorders and urinary collecting disorders, while coadministration of the alpha-1 adrenergic receptor antagonist and the anti-muscarinic agent is more effective for controlling overactive bladder (OAB) in BPH patients (3). Anti-muscarinic agents are known to inhibit bladder smooth muscle contraction, and may possibly also block the effects of muscarinic receptors on bladder epithelial cells (12,20). Bladder epithelial cells exhibit a number of properties similar to those of neurons (nociceptors/mechanoreceptors), and both types of cells share several signal transduction mechanisms to detect physiological stimuli. Examples of neuronal sensory receptors that have been identified in the bladder epithelium include receptors for purine (15), noradrenaline (4), and acetylcholine (12, 13). Recent studies have also shown that intravenous administration of alpha-1 adrenergic receptor antagonists inhibits adenosine triphosphate (ATP) release into the bladder lumen as well as bladder afferent nervous activity (9), while application of muscarinic agonists provokes ATP release from cultured bladder epithelial cells (14). These results suggest that both alpha-1 adrenergic receptor antagonist and anti-muscarinic agents inhibit ATP secretion from the bladder epithelium, and

Evidence for Bladder Urothelial Pathophysiology in Functional Bladder Disorders

“…Investigators found that urinary ATP was a better predictor than urinary NGF for detrusor overactivity in OAB [99]. Urinary ATP levels in OAB patients decreased after treatment with antimuscarinics [100], and a higher pretreatment urinary ATP level predicted a better response to antimuscarinic therapy. However, the sources of the urinary ATP (e.g., whether from the urothelium, suburothelium, nerves, and/or muscles) were not identified in these studies.…”

The regulation of distention-induced ATP release from urothelium by the adenylyl cyclase-cyclic AMP pathway

“…These studies indicate that urothelial ATP release could play a key role in both volume-and noxious stimulus-evoked reflexes. In fact, an excess of urothelial ATP release was detected in interstitial cystitis or overactive bladder, conditions accompanied by visceral hyperesthesia leading to frequent urination or bladder pain (2,(28)(29)(30). However, the precise signaling cascade involved in the pathological increase of urothelial ATP release remains unknown.…”

Store-operated Ca2+ entry suppresses distention-induced ATP release from the urothelium

“…In fact, an excess of urothelial ATP release was observed in interstitial cystitis (4,23,24). In a group of female overactive bladder patients, those with a high ratio of urinary ATP/creatinine showed a higher symptom score of urinary frequency than those with a low ratio (22). Therefore, elucidation of the molecular mechanisms underlying urothelial ATP release would contribute to drug development for the therapeutic alleviation of storage symptoms or bladder pain.…”