Vol 83, No 11 (2012)

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Overactive bladder – a new insight into the pathogenesis of its idiopathic form

Tomasz Rechberger, Andrzej Wróbel, Beata Kulik-Rechberger, Łukasz Nowakowski
Ginekol Pol 2012;83(11).


In the last few years cytokines have been shown to be the most important local cell signaling molecules, strongly involved in the pathogenesis of the overactive bladder symptoms. Proper bladder function is dependent on gap junction activity. The main gap junction proteins which can be found in bladder smooth muscle are Connexin 43 (Cx 43) and Connexin 45 (Cx45). Experimental studies focused on the influence of Basic Fibroblast Growth Factor on Connexin expression in bladder smooth muscle cells have shown an increased expression of Cx43, contrary to Cx45. Elevated level of Connexin 43 leads to overactivity of muscle fibers. It was also proved that expression of these proteins in tissues is modulated by cytokines. Regulation of the Cx43 promoter depends on an activating factor 1 (AP-1), cyclic monophosphate (cAMP) and retinoid concentration as well. AP-1 is induced by extracellular-signal-regulated kinases (ERK 1/2) through the activation of basic fibroblast growth factor (bFGF). Recent studies revealed that cytokine-induced modulation of gap junction plays an important role in the pathogenesis of OAB, whereas activation of sympathetic fibers via β adrenoreceptors (β –AR) causes relaxation of the bladder. The β-3 adrenoreceptors are divided into β-1, β-2, β-3 subtypes. β-3 adrenoreceptors have been found in fat and smooth muscle tissue. Density of β-3 AR is very high in urinary bladder detrusor. Activation of β-3 AR leads to the relaxation of smooth muscle fibers during the filling phase and is cAMP-dependent. Missense mutation of this receptor subtype in the human bladder, leading to the substitution of Tryptophan (Trp) by Arginine (Arg), occurs in about one-third of the world’s population. Studies have shown that about 50% of women with Trp 64 Arg polymorphism have OAB symptoms. Higher concentration of β3-AR with Trp 64 Arg polymorphism in bladders of women with diagnosed OAB is probably associated with a lower level of cAMP and weaker relaxation of the bladder smooth muscle. The role of the muscarinic receptors (M1-M5) in the pathogenesis of OAB has been widely described. Unfortunately, due to lack of selective muscarinic ligands, the function of each subtype of the receptor has not been fully elucidated yet. A mouse model lacking one or more muscarinic receptors types has been constructed recently. Animals were used to assess the real influence of various muscarinic receptors on bladder function. Studies have confirmed the importance of these receptors in the function of the urinary tract, offering a new insight in their mutual interactions and pathogenesis of OAB. Better understanding of these and new mechanisms may improve the process of diagnosis and treatment of the disease in the near future.

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