ATP released from the urothelium contributes to bladder
hyperactivity induced by acetic acid in the rat
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1
Instituto de Ciencias Biomedicas Abel Salazar - Universidade do Porto (ICBAS-UP), Laboratorio de Farmacologia e Neurobiologia, Unidade Multidisciplinar de Investigacao Biomedica (UMIB), Portugal
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2
CHP - HGSA, Serv. Urologia, Portugal
The bladder epithelium releases ATP in response to mechanical stimuli (and to chemical irritants), which may activate suburothelial sensory nerve fibers. Although the pathogenic mechanisms of bladder overactivity (OAB) are not fully understood, atropine-resistant purinergic reactivity increases in these patients (e.g. interstitial cystitis). Therefore, we aimed at investigating ATP release from the urothelium and the effects of this purine on bladder pressure and pelvic nerve activity in a in vivo rat model of hyperactive urinary bladder. Irritative cystometry (produced by the infusion of acetic acid, AA, 0.2-1% v/v) has been used to investigate new therapies from OAB.
AA (0.2-1%, for 15 min) concentration-dependently decreased the time (ICI, 67 to 81% of control) and the pressure threshold (PTh, 58 to 85% of control) for appearance of the micturition reflex. Using the luciferin- luciferase luminescence assay (Enliten ATP kit, Promega, USA), we showed that urinary ATP increased (52±7%, n=5) following the micturition reflex. The concentration of urinary ATP was significantly (P<0.05) enhanced in the presence of AA (1%, 297±25%, n=3), while the activity of urinary lactate dehydrogenase (LDH) remained unchanged. Increases in the voiding frequency caused by AA (0.2%) were enhanced by intravesical infusion of the P2X1 and P2X3 agonist, alpha,beta-methyleneATP (30 μM), and of the ecto- ATPase inhibitor, ARL67156 (200 μM). PPADS, applied either by intravesical infusion (30 μM) or by intravenous bolus (17 μmol/Kg), reduced AA-induced bladder hyperactivity. However, in contrast to alpha,beta-methyleneATP (30 μM), PPADS also decreased the contraction amplitude. Blockade of ADP- sensitive P2Y1 receptors with MRS2179 (1 μmol/Kg, i.v.) increased the voiding frequency secondary to AA (0.2 %), but it was devoid of effect on the contraction amplitude.
Although there is extensive literature indicating that many different types of purinoceptors are present in the lower urinary tract, the pathophysiological role of these receptors in OAB is still uncertain. Our results showed that ATP released from the urothelium play a role on bladder hyperactivity induced by intravesical infusion of acetic acid and that different subtypes of P2 purinoceptors regulate afferent nerve activity (P2X2/3 and P2Y1) and smooth muscle contractions (probably P2X2).
Work supported by FCT, Soc. Port. Urologia and Univ. Porto / Caixa Geral de Depósitos.
Conference:
11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009.
Presentation Type:
Poster Presentation
Topic:
Neuronal Communication
Citation:
Marinhas
JE,
Monteiro
D,
Silva
N,
Faria
M,
Duarte-Araujo
M,
Silva-Ramos
M and
Correia-de-Sa
P
(2009). ATP released from the urothelium contributes to bladder
hyperactivity induced by acetic acid in the rat.
Front. Neurosci.
Conference Abstract:
11th Meeting of the Portuguese Society for Neuroscience.
doi: 10.3389/conf.neuro.01.2009.11.148
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Received:
12 Aug 2009;
Published Online:
12 Aug 2009.
*
Correspondence:
Jose E Marinhas, Instituto de Ciencias Biomedicas Abel Salazar - Universidade do Porto (ICBAS-UP), Laboratorio de Farmacologia e Neurobiologia, Unidade Multidisciplinar de Investigacao Biomedica (UMIB), Porto, Portugal, josemarinhas@gmail.com