The effect of beta-3 adrenergic receptor agonist on micromotions of major pelvic ganglion disconnected rat bladder
Micromotion of bladder wall is suggested as an important component in production of detrusor overactivity. Beta-3 adrenergic receptor agonist is known to alleviate rodent bladder microcontractions by inhibiting afferent pathway. However, the exact action point is not clearly demonstrated. Rodent major pelvic ganglion (MPG) is known to have crucial role in controlling non-voiding detrusor contraction, and also reported to contain beta-3 adrenergic receptor. We have investigated the effect of beta-3 adrenergic receptor agonist (CL-316,243) on micromotion of major pelvic ganglion disconnected rat bladder.
Eighteen male Sprague-Dawley rats were used. Rats were anesthetized with 2% isoflurane in oxygen, and a lower midline incision was made. MPGs were found and were carefully removed under microscope. After a week of adaption period, PE-50 tubing was introduced into in the bladder and cystometry was performed by infusing physiological saline at a rate of 0.12ml/min. Rats were divided into 3 groups; CL-316,243 group, beta-3 adrenergic receptor antagonist (SR59230A) pretreated CL-316,243 group and oxybutinin group. The frequency of micromotion was checked at baseline, after intra-arterial administration of vehicle (saline), after intra-arterial administration of each target agent consecutively.
Micromotion frequency was significantly decreased after injection of CL-316.243 (2.2±3.5/10min) compared to baseline (7.5±2.6/10min) (P=0.005). There was no significant change of micromotion frequency in SR59230A pretreated CL-316.243 group (6.3±2.9/10min) compared to baseline (6.3±0.5/10min) (P=1.000). The number of micromotion after oxybutynin injection (3.2±3.1/10min) was not significantly different from that of baseline (5.7±3.1/10min) (P=0.059).
We could observe that beta-3 adrenergic receptor agonist have effect in alleviating micromotions of MPG disconnected rat bladder. These results also suggest that the major action point of the beta 3 adrenergic receptor agonist is in the bladder.