Enhancement of neurokinin A-induced smooth muscle contraction in human urinary bladder by mucosal removal and phosphoramidon: relationship to peptidase inhibition

European Journal of Pharmacology
F J WarnerE Burcher

Abstract

Neurokinin A (NKA) is potent in contracting the human detrusor muscle. Here, we have investigated whether these contractile responses are influenced by the presence of the mucosa, by the peptidase inhibitor phosphoramidon or by possible modulators, prostaglandins and nitric oxide. Contractile responses to neurokinin A were unaffected by indomethacin or N-omega-nitro-L-arginine, but were significantly reduced in strips containing mucosa. Phosphoramidon, an inhibitor of neutral endopeptidase 24.11 (neprilysin, CD10), was ineffective at 10 microM, but at 100 microM, significant increase in the maximum response was achieved by neurokinin A in detrusor strips with and without mucosa. In immunohistochemical studies, neutral endopeptidase immunoreactivity occurred in peripheral nerve trunks in the detrusor and in a fibrous meshwork in the subepithelial lamina propria. Our data indicate that neutral endopeptidase is present in bladder mucosa and detrusor, and support the concept that this metalloprotease and/or related enzymes are important in regulating the actions of tachykinins.

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Citations

Dec 10, 2003·Urology·Karl Erik Andersson
Aug 28, 2003·Clinical and Experimental Pharmacology & Physiology·Fiona J WarnerElizabeth Burcher
Dec 14, 2004·Life Sciences·Luz CandenasJocelyn N Pennefather
Mar 28, 2009·International Journal of Molecular Sciences·Toshio Mitsui, Hiroyuki Ohshima
Dec 17, 2004·Pharmacological Reviews·Karl-Erik Andersson, Alan J Wein
Dec 25, 2002·Physiological Genomics·Igor DozmorovRicardo Saban
Dec 12, 2002·Scandinavian Journal of Urology and Nephrology. Supplementum·K E Andersson

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