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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