A quantitative analysis of purinoceptor expression in the bladders of patients with symptomatic outlet obstruction

O’Reilly, Barry; Kosaka, Alan; Chang, Thomas K. H.; Ford, Anthony; Popert, R.; McMahon, Stephen B.

doi:10.1046/j.1464-410x.2001.02179.x

Cited by 95 publications

(78 citation statements)

References 26 publications

(32 reference statements)

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“…Primary expression of the P2X1 receptor is seen across the species, including humans (Lee et al, 2000;Vial and Evans, 2000;O'Reilly et al, 2001). For example in rats, P2X1 is the only subtype associated with the bladder detrusor smooth muscle membrane (Lee et al, 2000), and in P2X1 receptor deficient mice, ATP failed to evoke contraction or initiate inward currents (Vial and Evans, 2001).…”

Section: Rat Functional Responsesmentioning

confidence: 99%

“…Rapid responses to ATP are mediated by purinergic P2X receptors, which have been classified into 7 subtypes, which come together to form non-selective cation channels (Khakh et al, 2001). Variable profiles of expression have been detected using different methods in the bladder including from human tissue (O'Reilly et al, 2001;O'Reilly et al, 2002). Contraction is thought however to be mediated primarily via P2X1 receptors, since bladder contraction does not occur in mice having a P2X1 receptor deficiency (Vial and Evans, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Functional expression of muscarinic and purinoceptors in the urinary bladder of male and female rats and guinea pigs

Creed

Loxley

Phillips

2010

J. Smooth Muscle Res.

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Purpose: The objectives of this study were to compare the functional expression of muscarinic and purinergic receptors in the urinary bladder of 2 species, rat and guinea pig under comparable experimental conditions; and to test whether the receptors in males and females differ. Methods: Reverse transcription-polymerase chain reaction (RT-PCR) techniques were used to identify gene expression profiles in bladder smooth muscle (total n=8 rats, 7 guinea pigs) and mechanical responses to nerve stimulation and applied acetylcholine (ACh) in the presence of specific antagonists were used to identify functional receptor sub-types (total n=12 rats, 16 guinea pigs). Results: RT-PCR indicated that M2 and M3 were the predominant muscarinic receptor genes in both the male and female rat and guinea pig bladders. M) caused a significant reduction in the amplitude of the phasic response to nerve stimulation in all groups, and this effect was significantly greater in male vs. female rats. mRNA for the purinergic P2X1, P2X2, P2X4, P2X5 and P2X7 receptors was detected in both male and female rats, whereas P2X3 and P2X6 were inconsistently detected in male rats. The P2X1 purinoceptor antagonist pyridoxal-5'-phosphate-6-(2'-naphthylazo-6'-nitro-4', 8'-disulphonate) (PPNDS), only inhibited nerve induced contractions at high concentrations (up to 10 -4 M). Conclusions: While only minor functional differences were documented in cholinergic and purinergic bladder contractile responses between male and female animals, and between rats and guinea pigs, data such as presented in this study are critical in determining how relative functional contributions may change in the diseased state, providing valuable information towards new treatment options.

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Section: Rat Functional Responsesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional expression of muscarinic and purinoceptors in the urinary bladder of male and female rats and guinea pigs

Creed

Loxley

Phillips

2010

J. Smooth Muscle Res.

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“…In most species Ach is the main transmitter in the bladder with a variable contribution from ATP [7]. In the human bladder, Ach appears to be the sole or predominant transmitter in healthy detrusor tissue [8][9][10] but with ATP playing an enhanced role in the overactive bladder via P2X1 receptors [8,11]. Stronger contractile responses to ATP have also been detected in bladder tissues obtained from patients with overactive bladders compared with normal subjects suggesting the involvement of ATP in detrusor overactivity [12].…”

Section: Discussionmentioning

confidence: 99%

Pharmacologic responses of the mouse urinary bladder

2009

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AbstractThe aim of the study was to determine pathways involved in contraction and relaxation of the mouse urinary bladder. Mouse bladder strips were set up in gassed Krebs-bicarbonate solution and responses to various drugs and electrical field stimulation were obtained. Isoprenaline (b-receptor agonist) caused a 63% inhibition of carbachol precontracted detrusor (EC50=2nM). Carbachol caused contraction (EC50=0.3µM), responses were antagonised more potently by 4-DAMP (M3-antagonist) than methoctramine (M2-antagonist). Electrical field stimulation caused contraction, which was inhibited by atropine (60%) and less by guanethidine and α,β-methylene-ATP. The neurogenic responses were not potentiated by inhibition of nitric oxide synthase. Presence of an intact urothelium significantly depressed responses to carbachol (p=0.02) and addition of indomethacin and L-NNA to remove prostaglandin and nitric oxide production respectively did not prevent the inhibitory effect of the urothelium. In conclusion, b-receptor agonists cause relaxation and muscarinic agonists cause contraction via the M3-receptor. Acetylcholine is the main neurotransmitter causing contraction while nitric oxide has a minor role. The mouse and human urothelium are similar in releasing a factor that inhibits contraction of the detrusor muscle which is unidentified but is not nitric oxide or a prostaglandin. Therefore, the mouse may be used as a model to study the lower urinary tract.

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“…It is not expressed at all in fetal bladders 14 and its expression is not altered by bladder outlet obstruction, although the expression of all other known P 2 X receptors has changed in this condition, indicating a plasticity in the purinergic innervation of the bladder when obstruction occurs. 15 Also, in patients with interstitial cystitis, P 2 X 2 receptor expression was unchanged when compared to normal detrusor tissue, whereas P 2 X 3 receptor expression was decreased. 7 Thus, the only condition altering P 2 X 2 receptor expression was idiopathic detrusor overactivity.…”

Section: Introductionmentioning

confidence: 90%

Expression of purinergic P2X2-receptors in neurogenic bladder dysfunction due to spinal cord injury: a preliminary immunohistochemical study

et al. 2008

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Study design: Retrospective descriptive study. Objective: Although muscarinic receptors are the main targets for the treatment of detrusor overactivity today, anticholinergic therapy is not satisfying in a substantial percentage of patients. Recently, overexpression of P 2 X 2 receptors in patients with idiopathic overactive bladder was demonstrated, indicating that purinergic innervation may play an important role in the pathophysiology of detrusor overactivity. We evaluated the expression of P 2 X 2 receptors in patients with spinal cord lesions. Setting: German university hospital. Methods: By immunohistochemical staining, the frequency and intensity of P 2 X 2 expression in bladder specimens from 15 patients with suprasacral spinal cord lesion were compared to those from 11 patients with bladder disorders not related to spinal cord injury (overactive bladder: n ¼ 6; chronic nonobstructive retention: n ¼ 2; bladder tumour: n ¼ 3). Results: Specimens (12/15) from patients with spinal cord lesions and specimens (8/11) without spinal cord lesions demonstrated staining for P 2 X 2 receptors in the detrusor muscle and the urothelium. There was a tendency towards a stronger staining in specimens from patients with spinal cord lesion. Conclusion: Our pilot study gives a first hint that the P 2 X 2 expression in patients with suprasacral spinal cord injury seems to be comparable to the expression in patients with idiopathic overactive bladder. Therefore, P 2 X 2 receptors in detrusor tissue may be a future target for the treatment of detrusor overactivity.

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A quantitative analysis of purinoceptor expression in the bladders of patients with symptomatic outlet obstruction

Cited by 95 publications

References 26 publications

Functional expression of muscarinic and purinoceptors in the urinary bladder of male and female rats and guinea pigs

Functional expression of muscarinic and purinoceptors in the urinary bladder of male and female rats and guinea pigs

Pharmacologic responses of the mouse urinary bladder

Expression of purinergic P2X2-receptors in neurogenic bladder dysfunction due to spinal cord injury: a preliminary immunohistochemical study

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