Changes in Cholinergic and Purinergic Neurotransmission in the Diabetic Rabbit Bladder

Abstract

Background: Diabetes mellitus (DM)-associated alterations in bladder function have been attributed to changes in autonomic receptors and alterations in detrusor structure and function. The changes in cholinergic and purinergic neurotransmission in the DM rabbit bladder were evaluated. Materials and Methods: DM was induced with alloxan in adult male New Zealand White rabbits. At 6 months, detrusor and bladder neck muscle strips were obtained and mounted in organ baths. Transmural electrical field stimulation (EFS: supramaximal voltage, 0.1 ms duration, 10 s trains) was performed in the presence of atropine (10^-6 M) or alpha, beta-methylene ATP (10^-6 M), and after adding tetrodotoxin10^-6 M. Purinergic, alpha, beta-methylene ATP-sensitive, and cholinergic, atropine-sensitive, components were calculated independently and compared with those from controls. Results: Both normal and DM detrusor and bladder neck strips contracted in a frequency-dependent fashion in response to transmural EFS. A plot of EFS vs. detrusor contractility showed a decrease (ANOVA <0.001) in the cholinergic nerve-mediated component, whereas the purinergic nerve-mediated component was increased (ANOVA <0.001) in the DM detrusor compared to the control. The total EFS- and KCl-induced responses were unaltered in the DM group compared to the controls. There was no difference in purinergic, alpha, beta-methylene ATP-sensitive, and cholinergic, atropine-sensitive, components in strips from the bladder neck for both normal and DM rabbits. Conclusion: These results suggest that an enhancement of purinergic and a reduction of cholinergic neurotransmission occur in the detrusor muscle of the diabetic rabbit. These changes may contribute to the pathophysiology of diabetic cystopathy.