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The Journal of Neuroscience, 2001, 21:RC166:1-6

RAPID COMMUNICATION
Loss of Purinergic P2X3 and P2X5 Receptor Innervation in Human Detrusor from Adults with Urge Incontinence

Kate H. Moore1, Fiona R. Ray2, and Julian A. Barden2

1 The Detrusor Muscle Laboratory, Department of Urogynaecology, St. George Hospital, The University of New South Wales, New South Wales 2217, Australia and 2 Protein Structure Laboratory, The Institute for Biomedical Research and Department of Anatomy and Histology, The University of Sydney, New South Wales 2006, Australia

Activation of purinergic P2X receptors associated with the parasympathetic nerves that supply the human bladder smooth muscle (detrusor) is implicated in control of detrusor contractility. The relative abundance of all seven subtypes colocalized with synaptic vesicles on parasympathetic nerves was examined in specimens from normal adult bladder, infants, and in adults with overactive detrusor contractility and a diagnosis of idiopathic detrusor instability (IDI) to determine whether receptor distribution varied with age or in patients with incontinence. Alteration in control of detrusor innervation was examined with P2X subtype-specific antibodies and an antibody against synaptic vesicles, using immunofluorescence and confocal microscopy. Detrusor samples were taken from: controls, at cystectomy for cancer or cystoscopic biopsy for hematuria (n = 22; age 33-88), child bladder, at surgical correction of vesico-ureteric reflux (n = 21; age 4 months to 2 years), and adults with detrusor instability at cystoscopy-cystodistension (n = 18; age 30-81). Adult specimens contained muscle with large varicosities (1.2 µm) along parasympathetic nerves with colocalized patches of all P2X1-7 subtypes. Infant bladder revealed little evidence of P2X at age <9 months but approached adult levels at 2 years. Detrusor from IDI patients revealed selective absence of P2X3 and P2X5 beneath all the varicosities. This specific lack of P2X3 and P2X5 may impair control of detrusor contractility and contribute to the pathophysiology of urge incontinence.

Key words: purinergic P2X receptors; hypertonia; human urinary incontinence; detrusor instability; innervation; IDI bladder


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