Enhancement of neurokinin A-induced smooth muscle contraction in human urinary bladder by mucosal removal and phosphoramidon: relationship to peptidase inhibition.
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.
Warner
Fiona J
FJ
Department of Physiology and Pharmacology, University of New South Wales, NSW 2052, Sydney, Australia.
Shang
Fei
F
Millard
Richard J
RJ
Burcher
Elizabeth
E
D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008875:Middle Aged; D009092:Mucous Membrane / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015288:Neurokinin A / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D019459:Urothelium / Q000201:enzymology
D006020:Glycopeptides; D011480:Protease Inhibitors; D015288:Neurokinin A; D008666:Metalloendopeptidases; D015260:Neprilysin; C008890:phosphoramidon