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Interstitial cells and phasic activity in the isolated mouse bladder

Lookup NU author(s): Magdalini Lagou, Marcus Drake, Professor James Gillespie


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OBJECTIVE: To describe the distribution of interstitial cells (ICs, defined as cells which show an increase in cGMP in response to nitric oxide, NO) in the isolated mouse bladder, and changes in phasic contractile activity after exposure to a NO donor. MATERIALS AND METHODS: The whole bladder was removed from 17 female mice, killed by cervical dislocation. For immunohistochemistry (six mice) the bladder was incubated in carboxygenated Krebs' solution at 36°C, containing 1 mm of the phosphodiesterase inhibitor isobutyl-methyl-xanthine. Individual pieces of tissue were exposed to 100 μm of the NO donor diethylamine NONOate for 10 min; control tissues remained in Krebs' solution. Tissues were then fixed in 4% paraformaldehyde and processed for cGMP immunohistochemistry. Bladder pressure was measured in bladders from 11 mice; the bladders were cannulated via the urethra and suspended in a heated chamber containing carboxygenated Tyrode solution at 33-35°C and intravesical pressure recorded. All drugs were added to the solution bathing the abluminal surface. RESULTS: NO induced an increase in cGMP in cells in the outer layers of the bladder wall, forming two distinct types based on their location; cells lying on the surface of the muscle bundles (surface muscle ICs) and cells within the muscle bundles (intramuscular ICs). Cholinergic nerve fibres were identified by the expression of vesicular acetylcholine transporter and neuronal NO synthase (nNOS). Choline acetyltransferase- and nNOS-positive nerves also had high cGMP levels in response to 100 μm diethylamine NONOate. In vitro exposure of an isolated whole unstimulated bladder to 100 μm diethylamine NONOate had no effect on resting bladder pressure. When whole bladders were exposed to muscarinic stimulation (30-100 nm arecaidine) there was an initial large transient rise in pressure followed by complex phasic changes in pressure. Adding 100 μm diethylamine NONOate abolished this phasic activity. Interestingly, the phasic activity was inhibited midway between the peak and trough of a phasic cycle. Such a pattern of inhibition might reflect the complexity of the phasic activity involving both excitatory and inhibitory components. CONCLUSIONS: These data show the presence of NO/cGMP-sensitive ICs in the outer muscle layers of the mouse bladder. Activating these cells alters the pattern of muscarinic-induced phasic activity. We suggest that the role of the ICs in the outer muscle layers is to generate and modulate phasic activity. If so, then this is the first report of a functional role for ICs in the bladder. © 2006 The Authors.

Publication metadata

Author(s): Lagou M, Drake MJ, Markerink-Van Ittersum M, De Vente J, Gillespie JI

Publication type: Article

Publication status: Published

Journal: BJU International

Year: 2006

Volume: 98

Issue: 3

Pages: 643-650

ISSN (print): 1464-4096

ISSN (electronic): 1464-410X

Publisher: Wiley-Blackwell


DOI: 10.1111/j.1464-410X.2006.06255.x

PubMed id: 16925766


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