Publications by authors named "Neil G McKay"

The prevalence of lower urinary tract storage disorders such as overactive bladder syndrome and urinary incontinence significantly increase with age. Previous studies have demonstrated age-related changes in detrusor function and urothelial transmitter release but few studies have investigated how the urothelium and sensory pathways are affected. The aim of this study was to investigate the effect of ageing on urothelial-afferent signalling in the mouse bladder.

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Objective: To investigate the direct effect of onabotulinumtoxinA (OnaBotA) on bladder afferent nerve activity and release of ATP and acetylcholine (ACh) from the urothelium.

Materials And Methods: Bladder afferent nerve activity was recorded using an in vitro mouse preparation enabling simultaneous recordings of afferent nerve firing and intravesical pressure during bladder distension. Intraluminal and extraluminal ATP, ACh, and nitric oxide (NO) release were measured using the luciferin-luciferase and Amplex(®) Red assays (Molecular Probes, Carlsbad, CA, USA), and fluorometric assay kit, respectively.

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Increased phasic activity in the bladder smooth muscle of animal models and patients with detrusor overactivity has been suggested to underlie the pathophysiology of overactive bladder. Potassium (K+) channels are key regulators of bladder smooth muscle tone and thus may play a role in this altered phasic activity. In this study the effects of K+ channel modulators on the phasic activity of bladder strips from the streptozotocin-induced diabetic rat model of bladder dysfunction were investigated.

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Objective: • To investigate the role of c-kit-positive interstitial cells (ICCs) in mediating muscarinic receptor-induced phasic contractions of isolated bladder strips from streptozotocin(STZ)-induced diabetic rats and to confirm the expression and location of ICCs in the rat bladder.

Materials And Methods: • Bladders were removed from STZ-induced diabetic rats at 1, 4 and 12 weeks after induction of diabetes and from age-matched controls. • To investigate the functional role of ICCs in mediating phasic contractions, bladder strips were isolated from control and diabetic rats and mounted in tissue baths.

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Aims: Relaxation of detrusor muscle via β-adrenoceptors may contribute to urine storage during bladder filling. Thus there is increasing interest in β-adrenoceptor agonists as a potential treatment for detrusor overactivity. The role of the urothelium in bladder responses to β-adrenoceptor agonists is not yet clear, although we have shown that these agonists have a greater inhibitory effect on detrusor contraction when the urothelium is intact.

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This chapter describes a method of assaying rubidium (Rb(+)) efflux as a measure of potassium channel activity. In this assay, rubidium acts as a tracer for potassium movement across the cell membrane. HEK 293 cells expressing the alpha subunit of the human brain large-conductance, voltage-activated, calcium-sensitive potassium channel (BK channel) are loaded with Rb(+), washed, and then incubated under experimental conditions.

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The enteric sensory nervous system consists of extrinsic and intrinsic components. The cellular distribution of vanilloid receptor type 1 (VR1) and its relation to the intrinsic sensory neurones were studied in myenteric plexus-longitudinal muscle preparations of rat ileum and guinea-pig ileum and colon. VR1-immunoreactivity was localized on fine fibres and expressed by ganglionic cells.

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