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Lookup NU author(s): Dr Mohamed Khadra, Professor James Gillespie
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Objective. To measure the concentrations of nerve growth factor (NGF) in tissue biopsies taken from subjects with a normal bladder and from patients diagnosed to have idiopathic detrusor instability (associated with a reduction in the density of motor nerves), and to use an in vitro model to study the mechanisms of NGF expression. Materials and methods. Biopsy specimens were obtained during endoscopic and open surgery from patients undergoing routine bladder surgery. The patients were divided into two categories based upon urodynamic characterization. The NGF content in samples from 11 normal bladders and seven idiopathic unstable bladders were measured using an enzyme-linked immunosorbent assay. The mechanisms influencing net NGF production were explored using detrusor cells in vitro. Results. The mean (SEM) NGF content was significantly higher in unstable tissues, at 0.96 (0.05) pg/μg protein, than in the normal bladder, at 0.53 (0.05) pg/μg protein. In the cell model, acetylcholine (10 μmol/L), noradrenaline (1 and 10 μmol/L) and ATP (1 μmol/L) caused a significant increase in net NGF production; acetylcholine at 1 μmol/L had no effect. Direct stimulation of protein kinase C (PKC) by phorbol ester (33 ng/mL) or elevation of cAMP using forskolin (10 μmol/L) increased NGF, suggesting that at least two intracellular pathways (PKC- and PKA- dependent) are involved. The expression of c-Fos was increased by phorbol 12-myristate 13-acetate added before NGF, suggesting that c-Fos may be involved in regulating NGF production. Conclusion. These data suggest a role for NGF in the physiology and pathophysiology of the human bladder, and indicate some of the possible mechanisms which might regulate NGF production.
Author(s): Gillespie JI; Khadra MH; Tanner R; Chambers P
Publication type: Article
Publication status: Published
Journal: BJU International
Year: 2000
Volume: 85
Issue: 9
Pages: 1115-1119
ISSN (print): 1464-4096
ISSN (electronic): 1464-410X
Publisher: Wiley-Blackwell Publishing Ltd.
URL: http://dx.doi.org/10.1046/j.1464-410X.2000.00562.x
DOI: 10.1046/j.1464-410X.2000.00562.x
PubMed id: 10848707
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