SENSORY URINARY BLADDER ACTIVITY IN HEALTHY NON-ANESTHETIZED MOUSE AND IN A MOUSE WITH BLADDER OVERACTIVITY

Abstract

tension in organ bath filled with Krebs solution containing propranolol (1 μM) and prazosin (1 μM) in order to block 1/ 2-AR and 1-AR, respectively. Bladder contractions were elicited by electrical field stimulation (EFS; 800 mA, pulse duration 0.3 ms, train of pulses 2 s every 60 s) and concentrationresponse curves (CRC) to CL (0.01 to 100 μM) were obtained. CRCs were constructed in the presence of SR (0.3, 1, 3 μM), L (10 μM) or solvents, distilled water (DW) or DMSO 0.1%, respectively, incubated for 45 min. CL effects were expressed as % inhibition of basal response to EFS. RESULTS: CL ranging from 0.01 to 100 μM, significantly and concentration-dependently inhibited the neurogenic contractions (Figure 1). In presence of DW (n=13) or DMSO (n=6), the pIC50 values for CL were 6.9 ± 0.1 and 7.1 ± 0.1 with a maximal effect of -33 ± 1% and -28 ± 1%, respectively. SR shifted to the right the CRC to CL in a concentration dependent manner (Figure) generating a pA2 value of 6.8 (Schild plot slope = 1.1 ± 0.2). L (10 μM) also shifted significantly the CRC to CL to the right, resulting in a pKB = 7.0. The maximal relaxant effect was unaffected by the antagonists. CONCLUSIONS: Since under 1/ 2-AR blockade, CL-evoked relaxations of neurogenic contractions were competitively antagonized by SR and L with potencies similar to their affinities for cloned 3-AR, we confirm the functional role of 3-AR in mouse urinary bladder. This model is relevant to investigate the therapeutic potential of 3-AR agonist for the treatment of OAB in humans.