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No AccessJournal of UrologyInvestigative urology1 Feb 2006

Bladder Volume Alters Cholinergic Responses of the Isolated Whole Mouse Bladder

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    The isolated bladder expresses autonomous activity, which may contribute to the generation of lower urinary tract sensation or pathophysiology. We evaluated how the effect of a cholinergic agonist on autonomous activity alters with increasing volume and in the presence of substances known to modulate functional bladder capacity.

    Materials and Methods:

    The bladder of 22 adult female C57 black mice were mounted in whole organ tissue baths. Recordings of intravesical pressure were performed under standardized conditions at different bladder volumes.


    At low volume the muscarinic agonist arecaidine elicited an initial peak response, which subsided to a sustained steady state pressure. At high volume phasic pressure fluctuations were also apparent. An M2-receptor antagonist caused a significantly greater decrease in peak and steady state responses than in pressure fluctuations. An M3-receptor antagonist decreased all 3 components. α, β-Methylene adenosine triphosphate markedly decreased fluctuations, in contrast to norepinephrine, which eliminated the steady state response while preserving fluctuations.


    The response to cholinergic stimulation of the isolated bladder has 3 components. The initial tonic peak response increases with bladder distention and it is inhibited by M2 and M3 muscarinic receptor antagonists. The tonic steady state response does not vary with bladder volume and it is inhibited by M2 and M3-receptor antagonists, and by β3-adrenergic receptor agonists. Phasic fluctuations are minimal at low bladder volume, and with α, β-methylene adenosine triphosphate or an M3-receptor antagonist. Thus, the response to cholinergic stimulation varies with bladder volume. It can be differentially modulated by muscarinic antagonists and also by agents acting through nonmuscarinic receptors.


    • 1 : Developmental changes in spontaneous smooth muscle activity in the neonatal rat urinary bladder. Am J Physiol Regul Integr Comp Physiol2003; 285: R809. Google Scholar
    • 2 : Partial outlet obstruction enhances modular autonomous activity in the isolated rat bladder. J Urol2003; 170: 276. LinkGoogle Scholar
    • 3 : Autonomous activity in the isolated guinea pig bladder. Exp Physiol2003; 88: 19. Google Scholar
    • 4 : Localized modular contractions in the normal human bladder and in urinary urgency. BJU Int2005; 95: 1002. Google Scholar
    • 5 : Agonist- and nerve-induced phasic activity in the isolated whole bladder of the guinea pig: evidence for two types of bladder activity. Exp Physiol2003; 88: 343. Google Scholar
    • 6 : Urothelium-derived inhibitory factor(s) influences on detrusor muscle contractility in vitro. Br J Pharmacol2000; 129: 416. Crossref, MedlineGoogle Scholar
    • 7 : ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes—a possible sensory mechanism?. J Physiol1997; 505: 503. Google Scholar
    • 8 : Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci2002; 5: 856. Google Scholar
    • 9 : The role of the human bladder lamina propria myofibroblast. BJU Int2003; 91: 89. Google Scholar
    • 10 : Effects of resiniferatoxin desensitization of capsaicin-sensitive afferents on detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP in conscious rats. Naunyn Schmiedebergs Arch Pharmacol2003; 367: 473. Google Scholar
    • 11 : A myogenic basis for the overactive bladder. Urology1997; 50: 57. Crossref, MedlineGoogle Scholar
    • 12 : Role of interstitial cells and gap junctions in the transmission of spontaneous Ca2+ signals in detrusor smooth muscles of the guinea-pig urinary bladder. J Physiol2004; 559: 567. Google Scholar
    • 13 : Purinergic regulation of guinea pig suburothelial myofibroblasts. J Physiol2004; 559: 231. Google Scholar
    • 14 : Morphologies and projections of defined classes of neurons in the submucosa of the guinea-pig small intestine. Anat Rec A Discov Mol Cell Evol Biol2003; 272: 475. Google Scholar
    • 15 : The Enteric Nervous System. Edinburgh: Churchill Livingstone1987. Google Scholar
    • 16 : Volume-induced effects on the isolated bladder: a possible local reflex. BJU Int2004; 94: 1356. Google Scholar
    • 17 : The sensory-efferent function of capsaicin-sensitive sensory neurons. Gen Pharmacol1988; 19: 1. Google Scholar
    • 18 : Physiology of the urinary bladder and urethra. Ann Intern Med1980; 92: 312. Google Scholar
    • 19 : Model of peripheral autonomous modules and a myovesical plexus in normal and overactive bladder function. Lancet2001; 358: 401. Google Scholar
    • 20 : The autonomous bladder: a view of the origin of bladder overactivity and sensory urge. BJU Int2004; 93: 478. Google Scholar
    • 21 : New concepts in relation to urge and detrusor activity. Neurourol Urodyn1993; 12: 463. Google Scholar