/* */ PELVIPHARM - Human bladder tissue (control patients)
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Human bladder tissue (control patients)

Human bladder tissues advantages

  • In vitro investigation of human bladder function.
  • Useful to investigate the effect of drugs developed to improve overactive bladder.
  • Evaluation of the ability of drugs at modulating detrusor smooth muscle tone can be performed:
    • on cholinergic contractile response elicited by muscarinic pharmacological stimulation (carbachol) or by electrical field stimulation (EFS) which stimulates efferent nerve terminals present in the tissue.
    • on β-adrenergic relaxant response induced by pharmacological agents (norepinephrine).
    • on KCl response.
    • on others non adrenergic non cholinergic responses (purinergic, nitrergic…)
  • Evaluation of the influence of urothelium on the detrusor contractility.
  • Evaluation of the ability of drugs at modulating detrusor phasic contractile activity which represents an in vitro modelling of detrusor overactivity.
  • Evaluation of mRNA by RT-PCR or protein expression by, immunohistochemistry (IHC) or western-blot (WB), in parallel of organ bath studies.

Source of human tissues sample

  • Human normal bladder samples (dome with no macroscopic malignant tissue) are obtained from patients undergoing cystoprostatectomy for infiltrating bladder cancer. Donors with no known overactive bladder according to their medical chart are selected.

Figure 1: Photography of a section from human bladder wall.
Figure 1: Photography of a section from human bladder wall.


Figure 2: Original recording of contraction developed by human detrusor strips in response to EFS (300 mA, 5 s, 1 ms, 30 Hz). Effect of increasing and cumulative concentrations of the anti-muscarinic, oxybutynin. (Pelvipharm, internal data).
Figure 2: Original recording of contraction developed by human detrusor strips in response to EFS (300 mA, 5 s, 1 ms, 30 Hz). Effect of increasing and cumulative concentrations of the anti-muscarinic, oxybutynin. (Pelvipharm, internal data).


Figure 3: Influence of alfuzosin on the relaxation induced by norepinephrine on carbachol-induced bladder contractions. From Oger, S. et al. Eur Urol (2009) : May 3 [Epub ahead of print].
Figure 3: Influence of alfuzosin on the relaxation induced by norepinephrine on carbachol-induced bladder contractions. From Oger, S. et al. Eur Urol (2009) : May 3 [Epub ahead of print].

Endpoints

  • Evaluation of the capacity of a drug to inhibit detrusor smooth muscle contractions or detrusor phasic contractile activity.
  • Determination of potency (EC50) and efficiency (Emax) of a drug.
  • Determination of the affinity (pA2) of a drug for a human bladder receptor.
  • Evaluation of the influence of the urothelium.
Related Pelvipharm bibliography
Oger, S. et al.
BJP (2010) : 160(5):1135-43

Oger, S. et al. Eur Urol Supl 9(2) : 73-74 (EAU, 2010)

Oger, S. et al.
Eur Urol (2010) : 57(4):699-707

Oger, S. et al.
Eur Urol (2007) : 51(3):772-781

Darblade, B. et al.
Urology (2006) : 68(2):442-448

Darblade, B. et al.
World J. Urol (2005) : 23(2):147-151
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