Excitatory effects of neurokinin 2 and bombesin receptor peptide agonists vivo in urinary tract of rats with voiding dysfunctions

• Published in: The FASEB journal 2013-04, Vol.27 (S1)
• Main Authors: Kullmann, Florenta Aura, Zheng, Jihong, Wells, Grace, McKenna, David, Burgard, Ed, Thor, Karl
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.27.1_supplement.lb862

Abstract only Bladder function was examined in anesthetized and awake adult female Sprague Dawley rats. Voiding dysfunction models included STZ‐induced diabetic (streptozotocin; STZ; 65mg/kg i.p., 9–20 weeks post treatment), polyuria (5% sucrose‐fed; >;3 weeks post treatment) and spinal cord injured (SCI; T8‐T9 cut; acute or 3 days – 6 weeks post SCI) rats. Telemetry transmitters were implanted into polyuria group to measure bladder pressure in freely moving rats. [Lys 5 ,MeLeu 9 ,Nle 10 ]‐NKA(4–10) (LMN‐NKA), a neurokinin 2 receptor (NK2R) agonist, gastrin‐releasing peptide (GRP), a bombesin receptor 2 (BBR2) agonist, and neuromedin B (NMB), a BBR1 agonist, were delivered via jugular vein catheters. In urethrane anesthetized STZ and control rats, LMN‐NKA (0.1–100μg/kg), GRP (0.1–300μg/kg) and NMB (0.1–300μg/kg) dose dependently increased bladder contraction (BC, up to 4x) and micturition frequency. In STZ rats, LMN‐NKA reduced residual volume by half. In acute anesthetized SCI rats, LMN‐NKA (>;10μg/kg) induced urine release (voiding efficiency ~40%). In awake polyuria rats, LMN‐NKA and GRP (1–100μg/kg) induced BC that was often associated with voiding. In awake SCI rats, LMN‐NKA (100μg/kg) and GRP (100, 300μg/kg) triggered voiding in 25 – 80% of rats. Activation of NK2R and BBRs enhanced or triggered voiding in naïve rats and in several models of voiding dysfunction including STZ and SCI rats.