Concomitant alteration in number and affinity of P 2 X and muscarinic receptors are associated with bladder dysfunction in early stage of diabetic rats.

Objectives: To investigate time course of bladder dysfunction and concurrent changes in number and affinity of the muscarinic and P ₂ X receptor in the early stage of streptozotocin (STZ)-induced diabetic rats.
Materials and Methods: Diabetic rats were prepared by the intraperitoneal injection of 50 mg/kg of STZ to 7-week-old female Wistar rats. We performed recording of 24-h voiding behavior and cystometry at 1, 4, 8, and 12 weeks after the induction of diabetes. A muscle strip experiments with electrical field stimulation (EFS), carbachol, and α,β-methylene adenosine 5'-triphosphate (α,β-MeATP) were also performed at the same time-points. Additionally, concurrent changes in number and affinity of bladder muscarinic and P ₂ X receptor were measured by a radioreceptor assay using [N-methyl- ³ H] scopolamine methyl chloride ([ ³ H]NMS) and α,β-methylene-ATP (2,8- ³ H) tetrasodium salt ([ ³ H]α,β-MeATP).
Results: In STZ-induced diabetic rats, polydipsic polyuric pollakiuria were noted on recording of 24-h voiding behavior from early stage. Also, the residual urine volume markedly increased in diabetic rats on cystometry. In the muscle strip experiment, the detrusor contractions induced by EFS, carbachol, and α,β-MeATP were enhanced in STZ-induced diabetic rats. Based on the radioreceptor assay, the maximum number of sites (Bmax) for the specific binding of [ ³ H]NMS and [ ³ H]α,β-MeATP was concurrently increased in the bladder from diabetic rats.
Conclusion: Increased bladder contractility is found in early stage of diabetic rats. Then, bladder dysfunction is associated with increased number of muscarinic and P ₂ X receptors in STZ-induced diabetic rats.