Impaired response to chemical irritation of the urinary tract in mice withdisruption of the preprotachykinin gene

Previous studies demonstrated that acute irritation of the lower urinary tr act (LUT) induces the expression of the immediate early gene, c-fos, in lum bo-sacral spinal cord neurons 'J. Neurosci. 12 (1992) 4878' 'Am. J. Physiol . 265 (1993) 326' 'Somatosens. Mot. Res. 15 (1998) 5'. This effect was medi ated in part by activation of capsaicin-sensitive bladder afferents 'Am. J. Physiol. 265 (1993) 326'. Here we investigate the role of preprotachykinin gene products (neurokinin A and substance P) in the response to bladder ir ritation in urethane-anesthetized mice. Acute irritation of the LUT (intrav esical acetic acid) induced smaller numbers of Fos-positive neurons in the spinal cord of mice with a mutated preprotachykinin gene than in wild type mice. Increased Fos expression following LUT irritation or a sham operation in wildtype mice was also significantly reduced by pretreatment with the N K2 antagonist, MEN 11420, but Fos expression in mutant mice was not altered by the antagonist. During cystometrograms, a significantly higher percenta ge (83%) of mutant mice exhibited urinary retention and overflow incontinen ce as compared to wild type controls. These findings suggest an involvement of tachykinins and NK2 receptors in the response to chemical irritation of the LUT in mice and also suggest that tachykinins contribute to the regula tion of normal reflex bladder activity. (C) 2001 Elsevier Science Ireland L td. All rights reserved.