Involvement of connexins 43 and 45 in functional mechanism of human detrusor overactivity in neurogenic bladder.

To assess the involvement of connexins (Cxs) 43 and 45 in the selective inhibition of detrusor contractions in patients with neurogenic detrusor overactivity (NDO). Detrusor strips with and without mucosa were obtained from patients undergoing cystectomy for either neurogenic bladder with NDO refractory to pharmacologic treatment or bladder cancer with no overactive bladder symptoms (ie, control group). The strips were isometrically mounted in organ baths. The effects of the selective inhibitors Cxs 43 and 45 on carbachol-induced contractions of bladder strips were assessed. Overall, 47 patients with a median age of 61 years (range 19-83) were included. The female-to-male ratio was 0.42. Selective inhibitors of Cxs 43 and 45 significantly inhibited carbachol-induced contractions of bladder strips from patient with NDO (P <.01) but had no effect in the control group. When tested without mucosa, the effect of the Cx 43 inhibitor in the NDO patient strips was abolished, but it remained unchanged with the Cx 45 inhibitor (P <.05). The pharmacologic modulation of Cx-mediated intercellular communication, targeting Cxs 43 and 45, is directly involved in the functional mechanism of NDO and might represent a future target for the treatment of NDO. Copyright © 2013 Elsevier Inc. All rights reserved.

Citation

Véronique Phé, Delphine Behr-Roussel, Stéphanie Oger-Roussel, Morgan Rouprêt, Emmanuel Chartier-Kastler, Thierry Lebret, Gilles Karsenty, Eva Compérat, Philippe Camparo, François Giuliano. Involvement of connexins 43 and 45 in functional mechanism of human detrusor overactivity in neurogenic bladder. Urology. 2013 May;81(5):1108.e1-6

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PMID: 23490518

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