Detrusor overactivity induced by intravesical application of adenosine 5 '-triphosphate under different delivery conditions in rats

Objectives. We investigate the effects of intravesical application of adenosine 5'-triphosphate (ATP) on bladder activity to elucidate the role of urothelial barrier function and ecto-ATPase activity in the ATP-mediated mechanism inducing detrusor overactivity. Methods. Continuous cystometry by an intravesical catheter inserted from the bladder dome was performed in conscious female rats. Results. ATP solutions adjusted to pH 6.0 did not elicit significant detrusor overactivity at a concentration of 60 mM. However, in bladders pretreated with protamine sulfate (10 mg/mL) to increase urothelial permeability, ATP solution (pH 6.0) induced detrusor overactivity by decreasing the intercontraction intervals. These irritant effects of ATIP after protamine treatment were antagonized by P2X receptor antagonists, such as pyridoxal-5-phosphate-6-azophenyl-2',4-disulfonic acid (70 mu mol/kg) and 2',3'-O-(2,4,6, trinitrophenyl) ATP (30 mu mol/kg). These were also suppressed in rats pretreated with systemic capsaicin (125 mg/kg subcutaneously). Alpha,beta-methylene ATP (5 mM, pH 6.0) or ATP (60 mM, pH6) after intravesical infusion of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (5 mM, pH 6.0), an ecto-ATPase inhibitor, induced detrusor overactivity without protamine pretreatment, but the reduction in intercontraction intervals was smaller compared with that with ATP after protamine treatment. Conclusions. Low permeability of bladder epithelium and ecto-ATPase activity can prevent ATP activation of subepithelial P2X receptors to induce bladder overactivity. Thus, enhanced penetration of endogenous ATIP owing to urothelial damage may contribute to urinary frequency and bladder pain in hypersensitive bladder disorders such as interstitial cystitis.</p

Role of the Anterior Cingulate Cortex in the Control of Micturition Reflex in a Rat Model of Parkinson's Disease

Purpose: The present study examined dynamic changes in neural activity of the anterior cingulate cortex (ACC) and the midbrain periaqueductal gray (PAG) during the micturition reflex in a Parkinson's disease (PD) model as well as the effects of direct stimulation of the ACC on the micturition reflex. Materials and Methods: Electrodes were inserted into the ACC or the PAG, and the effects of intravenous (i.v.) administration of ZM24138 (ZM: adenosine A2A receptor antagonist) on the pelvic nerve evoked field potentials were examined. The effect of electrical stimulation of the ACC was also examined. Results: PD rats showed bladder overactivity evidenced by a significant decrease in intercontraction intervals (ICI) compared with sham rats. I.v. administration of ZM increased ICI in both groups with the inhibitory effects being greater in PD; and dose-dependently increased the amplitude of evoked potentials in the ACC of PD rats but not in sham rats. I.v. administration of ZM reduced the evoked potential amplitude in the PAG of both groups with the inhibitory effects being greater in PD vs. sham rats. Electrical stimulation of the ACC significantly increased ICI. Conclusions: These results suggest that ACC neurons have an inhibitory role in bladder control because neural activity in the ACC was significantly increased along with suppression of bladder overactivity after ZM administration in the PD model, and the stimulation of the ACC inhibited the micturition reflex. Understanding the roles of the ACC in the modulation of micturition could provide further insights into the pathophysiology of OAB