Expression of ß-adrenergic receptor subtypes in human normal and dilated ureter.

BACKGROUND: Ureter peristalsis is a basic physiological function regulated by myogenic and neurogenic factors. The distribution and function of ß-adrenergic receptors (ß-AR) in the human ureter remain unknown. The aim of this study was to investigate the expression of ß-AR subtypes in the normal and dilated human ureter. METHODS: The upper, middle, and lower segments of normal and dilated ureters were collected from patients undergoing surgery for carcinoma of the kidney and upper urinary tract and ureteral stenosis. The mucosa and muscular layers were separated. Expression of ß1-AR, ß2-AR, and ß3-AR mRNA and protein levels were detected by real-time PCR, western blot, and immunohistochemistry. RESULTS: In both mucosa and muscular layers, the mRNA and protein expressions of ß1-AR, ß2-AR, and ß3-AR were lower in the dilated ureter compared with the normal ureter. ß1-AR mRNA was significantly decreased (by 76.64%; P < 0.01) in the mucosa layer of the middle segment of the dilated ureter. ß1-AR and ß3-AR mRNA were significantly decreased (by 75.53 and 53.62%, respectively; P < 0.01) in the muscular layer of the lower segment of the dilated ureter. Similar findings were observed for protein expression. CONCLUSIONS: The downregulation of ß-ARs after ureter dilation, particularly for ß1-AR and ß3-AR in the muscular layer, suggests a potential compensatory mechanism involving increased contraction of the ureter to push urine through the obstruction. Thus, ß-ARs may be a potential target for treatment of ureter obstruction.

Intrathecal administration of TRPA1 antagonists attenuate cyclophosphamide-induced cystitis in rats with hyper-reflexia micturition.

BACKGROUND: The activation of TRPA1 channel is implicated in hyper-reflexic micturition similar to overactive bladder. In this study, we aimed to investigate the effects of blocking TRPA1 via intrathecal administration of antagonists on the afferent pathways of micturition in rats with cystitis. METHODS: The cystitis was induced by intraperitoneal cyclophosphamide administration. Cystometry was performed in control and cystitis rats, following the intrathecal injection of the TRPA1 antagonists HC-030031 and A-967079. Real-time PCR, agarose gel electrophoresis, western blotting and immunohistochemistry were used to investigate the levels of TRPA1 mRNA or protein in the bladder mucosa and L6-S1 dorsal root ganglia (DRG). RESULTS: Edema, submucosal hemorrhaging, stiffness and adhesion were noted during removal of the inflamed bladder. The expression of TRPA1 mRNA and protein was higher in the cystitis group in both the mucosa and DRG, but the difference was significant in the DRG (P < 0.05). Intrathecal administration of HC-030031 and A-967079 decreased the micturition reflex in the cystitis group. A 50 µg dose of HC-030031 increased the intercontraction interval (ICI) to 183 % of the no-treatment value (P < 0.05) and decreased the non-voiding contraction (N-VC) to 60 % of control (P < 0.01). Similarly, the treatment with 3 µg A-967079 increased the ICI to 142 % of the control value (P < 0.05) and decreased the N-VC to 77 % of control (P < 0.05). The effects of both antagonists weakened approximately 2 h after injection. CONCLUSIONS: The TRPA1 had a pronounced upregulation in DRG but more slight in mucosa in rat cystitis. The blockade of neuronal activation of TRPA1 by intrathecal administration of antagonists could decrease afferent nerve activities and attenuated detrusor overactivity induced by inflammation.