P 3.7. Urinary bladder responses to neurokinin A in aromatase knockout and wild-type mice

• Published in: Neuropeptides (Edinburgh) Vol. 42; no. 4; p. 481
• Main Authors: Kerr, K P, Liu, J, Gray, K T, Brown, R M, Chess-Williams, R, Jones, ME, Simpson, E R
• Format: Journal Article
• Language: English
• Published: 01.08.2008
• ISSN: 0143-4179

Aim of investigation. Oestrogen receptors are present in both the detrusor and mucosal layers of the mouse bladder [1]. The effectiveness of oestrogen in treating incontinence is controversial and recent evidence suggests that oestrogen may aggravate incontinence [2]. Since aromatase is required to produce oestrogens, the aromatase knockout mouse provides an ideal model for studying the effects of oestrogen. The aim was to compare responses to neurokinin A (NKA) in bladder strips of wild-type and knockout female mice as well as in intact preparations and those with the mucosa removed. Methods. One milliliter strips were cut off the dome and base of the bladder to yield a ring of tissue which, when opened, provided a strip (9 x 2.5 mm) that was set up under 2 g wt tension in 3 ml siliconized organ baths of Krebs-Henseleit solution, bubbled with 95% O sub(2), 5% CO sub(2) at 37 degree C and equilibrated for 45 min. Both intact preparations and those with the mucosa removed were used. Cumulative concentration-response curves to NKA were constructed. Responses were measured as force per mg (g/mg) of dry weight of detrusor with the mucosa removed for all preparations. Results. While there was no significant difference between the pEC sub(50) values for NKA in the wild-type and knockout mice, the Emax was significantly (P < 0.05) higher in the wild-type mice (2.90 plus or minus 0.35, n = 9 vs 1.55 plus or minus 0.17, n = 8 g/mg). The E sub(max) value was also significantly higher (P < 0.05) in intact wild-type bladders than those with the mucosa removed (2.90 plus or minus 0.35, n = 9 vs 1.29 plus or minus 0.08, n = 8 g/mg). In contrast, there was no significant difference in E sub(max) values between intact (n = 8) and mucosa-free (n = 10) knockout mice. Conclusions. Oestrogen appears to enhance contractile responses to NKA in the female mouse bladder and the mode of action may reside in the mucosa.