Role of p75NTR in female rat urinary bladder with cyclophosphamide-induced cystitis

Previous studies demonstrated changes in urinary bladder neurotrophin content and upregulation of neurotrophin receptors, TrkA and the p75 neurotrophin receptor (p75NTR), in micturition reflex pathways after cyclophosphamide (CYP)-induced cystitis. p75NTR can bind nerve growth factor (NGF) and modulate NGF-TrkA binding and signaling. We examined p75NTR expression and the role of p75NTR in the micturition reflex in control and CYP-treated rats. p75NTR Immunoreactivity was present throughout the urinary bladder. CYP-induced cystitis (4 h, 48 h, chronic) increased ( P ≤ 0.05) p75NTR expression in whole urinary bladder as shown by Western blotting. The role of p75NTR in bladder function in control and CYP-treated rats was determined using conscious cystometry and immunoneutralization or PD90780, a compound known to specifically block NGF binding to p75NTR. An anti-p75NTR monoclonal antibody or PD90780 was infused intravesically and cystometric parameters were evaluated. Both methods of p75NTR blockade significantly ( P ≤ 0.05) decreased the intercontraction interval and void volume in control and CYP-treated rats. Intravesical infusion of PD90780 also significantly ( P ≤ 0.001) increased intravesical pressure and increased the number of nonvoiding contractions during the filling phase. Control intravesical infusions of isotype-matched IgG and vehicle were without effect. Intravesical instillation of PD90780 significantly ( P ≤ 0.01) reduced the volume threshold to elicit a micturition contraction in control rats (no inflammation) and CYP-treated in a closed urinary bladder system. These studies demonstrate 1) ubiquitous p75NTR expression in urinary bladder and increased expression with CYP-induced cystitis and 2) p75NTR blockade at the level of the urinary bladder produces bladder hyperreflexia in control and CYP-treated rats. The overall activity of the urinary bladder reflects the balance of NGF-p75NTR and NGF-TrkA signaling.

Download Full-text

A possible role of the cholinergic and purinergic receptor interaction in the regulation of the rat urinary bladder function

Journal of Muscle Research and Cell Motility ◽

10.1007/s10974-012-9285-x ◽

2012 ◽

Vol 32 (6) ◽

pp. 421-431 ◽

Cited By ~ 3

Author(s):

Ágnes Jenes ◽

Ferenc Ruzsnavszky ◽

Andrea Telek ◽

Gyula P. Szigeti ◽

László Csernoch

Keyword(s):

Urinary Bladder ◽

Purinergic Receptor ◽

Bladder Function ◽

Receptor Interaction ◽

Rat Urinary Bladder

Download Full-text

Role for pAKT in rat urinary bladder with cyclophosphamide (CYP)-induced cystitis

AJP Renal Physiology ◽

10.1152/ajprenal.00556.2010 ◽

2011 ◽

Vol 301 (2) ◽

pp. F252-F262 ◽

Cited By ~ 15

Author(s):

Lauren Arms ◽

Margaret A. Vizzard

Keyword(s):

Urinary Bladder ◽

Bladder Capacity ◽

Intravesical Instillation ◽

Bladder Function ◽

Rat Urinary Bladder ◽

Akt Phosphorylation ◽

Somatic Pain ◽

Time Points ◽

Bladder Inflammation ◽

Female Wistar Rats

AKT phosphorylation following peripheral nerve injury or inflammation may play a role in somatic pain processes and visceral inflammation. To examine such a role in micturition reflexes with bladder inflammation, we induced bladder inflammation in adult female Wistar rats (200–300 g) by injecting cyclophosphamide (CYP) intraperitoneally at acute (150 mg/kg; 4 h), intermediate (150 mg/kg; 48 h), and chronic (75 mg/kg; every third day for 10 days) time points. Western blot analyses of whole urinary bladders showed significant increases ( P ≤ 0.01) in phosphorylated (p) AKT at all time points; however, the magnitude of AKT phosphorylation varied with duration of CYP treatment. Immunohistochemical analyses of pAKT immunoreactivity (pAKT-IR) in cryostat bladder sections demonstrated duration-dependent, significant ( P ≤ 0.01) increases in pAKT-IR in both the urothelium and detrusor smooth muscle of CYP-inflamed bladders. Additionally, a suburothelial population of pAKT-IR macrophages (CD68-, MAC2-, and F4/80-positive) was present in chronic CYP-treated bladders. The functional role of pAKT in micturition was evaluated using open, conscious cystometry with continuous instillation of saline in conjunction with administration of an inhibitor of AKT phosphorylation, deguelin (1.0 μg/10 μl), or vehicle (1% DMSO in saline) in control (no inflammation) and CYP (48 h)-treated rats. Bladder capacity, void volume, and intercontraction void interval increased significantly ( P ≤ 0.05) following intravesical instillation of deguelin in CYP (48 h)-treated rats. These results demonstrate increased AKT phosphorylation in the urinary bladder with urinary bladder inflammation and that blockade of AKT phosphorylation in the urothelium improves overall bladder function.

Download Full-text