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Isolated Bladder (isolated + bladder)

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Medical Sciences	100%

Selected Abstracts

Phosphodiesterase-linked inhibition of nonmicturition activity in the isolated bladder

BJU INTERNATIONAL, Issue 9 2004
J.I. Gillespie
Over the past few months Gillespie has published several papers in the BJU International investigating the overactive bladder and BOO, using novel models and theories. This next paper continues these concepts and shows that the mechanisms influencing the frequency of agonist-induced phasic activity in the isolated bladder model is slowed by cAMP. These findings will have important implications in future pharmacological strategies in the overactive bladder. OBJECTIVE To explore the influence of intracellular cAMP on phasic activity in the isolated bladder (phasic rises in intravesical pressure associated with waves of contraction and local stretches that can be activated by muscarinic or nicotinic agonists), as it has been argued that this activity underlies nonmicturition contractions, and that it contributes to the generation and modulation of afferent nerve activity. MATERIALS AND METHODS Isolated whole bladders from female guinea pigs (270,300 g) were cannulated via the urethra and suspended in a chamber containing oxygenated Tyrode solution at 33,35 °C. Bladder pressure was recorded and pharmacological agents added to the solution bathing the abluminal surface of the bladder. RESULTS Forskolin (1,3 µmol/L), an activator of adenyl cyclase, reduced the frequency and amplitude of the phasic activity induced by the muscarinic agonist arecaidine (300 nmol/L). There were similar changes in frequency and amplitude in bladders exposed to the nonspecific phosphodiesterase (PDE) inhibitor iso-butyl-methyl-xanthene (IBMX). The actions of specific PDE inhibitors were explored to assess which isoenzymes might be responsible for regulating phasic activity. ENHA (PDE-2), zaprinast (PDE-5, -6, -8, -9 and -11) and siguazodan (PDE-3) had no effect. Zardavarine (PDE-3, -4) and Ro 20-1724 (PDE-4) reduced both the frequency and amplitude of the phasic activity. Nerve-mediated rises in intravesical pressure were also inhibited by Ro 20-1724, and the inhibition was more pronounced at 6.5 Hz than at 30 Hz stimulation. Ro 20-1724 inhibited nerve-mediated fluctuations induced by prolonged (200 s) stimulation at 6.5 Hz. CONCLUSION The mechanisms influencing the frequency of agonist-induced phasic activity in the isolated bladder are slowed by cAMP. Degradation of intracellular cAMP in the cells responsible for phasic activity appears to involve primarily PDE-4. The importance of these observations in relation to the overall physiological regulation of the bladder are discussed, and the possible importance of these findings in the development of pharmacological strategies to modulated bladder activity reviewed. [source]

Comparison study of autonomous activity in bladders from normal and paraplegic rats,,

NEUROUROLOGY AND URODYNAMICS, Issue 4 2006
Thomas Gevaert
Abstract Aim To identify differences in the pattern of pressure generated by isolated bladders from normal and paraplegic rats. Materials and Methods Nine female Wister rats were made paraplegic by spinal cord transsection at the vertebral level T8-T9 and sacrificed between D21 and D28. A further group (n,=,9) was used as a control group. Each bladder was excised and placed in an organ bath where intravesical pressures were measured. Pressure changes were divided in two well-defined groups: macro-transients and spikes. The effects of intravesical volume load and muscarinic (M) agonists were studied. Results We demonstrated a higher frequency, a longer duration, and a higher variance of duration in macro-transients in the neurogenic group. Intravesical volume load influenced the amplitude and frequency of macro-transients in both groups similarly. The effects of the muscarinic (M2)-selective agonist arecaïdine were different in neurogenic bladder; the effects of the non-selective muscarinic (M)-agonist carbachol were similar in both groups. Conclusion We showed that the pattern of autonomous activity was significantly different between normal and neurogenic rat bladders. We also found evidence for alterations in the muscarinic response of isolated neurogenic rat bladders. This model offers an exciting new research tool to evaluate the detrusor activity in neurogenic and normal conditions. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc. [source]

Effects of imatinib mesylate (Glivec®) as a c-kit tyrosine kinase inhibitor in the guinea-pig urinary bladder

NEUROUROLOGY AND URODYNAMICS, Issue 3 2006
Yasue Kubota
Abstract Aims In the gastrointestinal tract, slow wave activity in smooth muscle is generated by the interstitial cells of Cajal (ICC). Detrusor smooth muscle strips of most species show spontaneous contractions which are triggered by action potential bursts, however, the pacemaker mechanisms for the detrusor are still unknown. Recently, ICC-like cells have been found in guinea-pig bladder, using antibodies to the c-kit receptor. We have investigated the effects of Glivec, a c-kit tyrosine kinase inhibitor, on spontaneous action potentials in guinea-pig detrusor and intravesical pressure of isolated guinea-pig bladders. Methods Changes in the membrane potential were measured in guinea-pig detrusor smooth muscle using conventional microelectrode techniques. Pressure changes in the bladder were recorded using whole organ bath techniques. Results Smooth muscle cells in detrusor muscle bundles exhibited spontaneous action potentials, and spontaneous pressure rises occurred in isolated bladders. Glivec (10 ,M) converted action potential bursts into continuous firing with no effects on the shape of individual action potentials. Glivec (>50 ,M) reduced the amplitude of spontaneous pressure rises in the whole bladder in a dose dependent manner and abolished spontaneous action potentials in detrusor smooth muscle cells. Conclusions The results suggest that ICC-like cells may be responsible for generating bursts of action potentials and contractions in detrusor smooth muscle. Drugs inhibiting the c-kit receptor may prove useful for treating the overactive bladder. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc. [source]