Localization of M2 and M3 muscarinic receptors in human bladder disorders and their clinical correlations.
OBJECTIVE
We studied the cellular localization of muscarinic receptor subtypes 2 and 3 in the human bladder and related any changes in overactive and painful bladder syndromes to measures of clinical dysfunction.


METHODS
Bladder specimens obtained from patients with painful bladder syndrome (11), idiopathic detrusor overactivity (12) and from controls with asymptomatic microscopic hematuria (16) were immunostained using specific antibodies to muscarinic receptor subtypes 2 and 3, and to vimentin, which is a marker for myofibroblasts. Immunostaining results were quantified with computerized image analysis and correlated with clinical dysfunction using frequency and urgency scores.


RESULTS
Muscarinic receptor subtype 2 and 3 immunoreactivity was observed in the urothelium, nerve fibers and detrusor layers. In addition, strong myofibroblast-like cell staining, similar to vimentin, was present in the suburothelial region and detrusor muscle. A significant increase in suburothelial myofibroblast-like muscarinic receptor subtype 2 immunoreactivity was seen in patients with painful bladder syndrome (p = 0.0062) and idiopathic detrusor overactivity (p = 0.0002), and in muscarinic receptor subtype 3 immunoreactivity in those with idiopathic detrusor overactivity (p = 0.0122) with a trend in painful bladder syndrome. Muscarinic receptor subtype 2 and 3 immunoreactivity significantly correlated with the urgency score (p = 0.0002 and 0.0206, respectively) and muscarinic receptor subtype 2 immunoreactivity correlated with the frequency score (p = 0.0029). No significant difference was seen in urothelial and detrusor muscarinic receptor subtypes 2 and 3 or vimentin immunostaining.


CONCLUSIONS
To our knowledge this is the first study to show the cellular localization of muscarinic receptor subtypes 2 and 3 in the human bladder. The increase in muscarinic receptor subtypes 2 and 3 immunostaining in myofibroblast-like cells in clinical bladder syndromes and its correlation with clinical scores suggests a potential role in pathophysiological mechanisms and the therapeutic effect of anti-muscarinic agents.
Mukerji
Gaurav
G
Peripheral Neuropathy Unit, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
Yiangou
Yiangos
Y
Grogono
Joanna
J
Underwood
Jenny
J
Agarwal
Sanjiv K
SK
Khullar
Vikram
V
Anand
Praveen
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005347:Fibroblasts / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009130:Muscle, Smooth / Q000737:chemistry / Q000473:pathology; D009412:Nerve Fibers / Q000737:chemistry; D010146:Pain; D043585:Receptor, Muscarinic M2 / Q000032:analysis*; D043587:Receptor, Muscarinic M3 / Q000032:analysis*; D013577:Syndrome; D001743:Urinary Bladder / Q000737:chemistry* / Q000294:innervation / Q000473:pathology; D001745:Urinary Bladder Diseases / Q000378:metabolism*; D014549:Urinary Incontinence / Q000378:metabolism*; D019459:Urothelium / Q000737:chemistry / Q000473:pathology
D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3