P2x Receptors and Their Role in Female Idiopathic Detrusor Instability

O’Reilly, Barry; Kosaka, Alan; KNIGHT, GILLIAN F.; Chang, Thomas K. H.; Ford, Anthony; Rymer, Janice; Popert, Rick; Burnstock, Geoffrey; McMahon, Stephen B.

doi:10.1016/s0022-5347(05)65403-1

Cited by 168 publications

(103 citation statements)

References 36 publications

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“…63 ATP has also been implicated as a neurotransmitter in the generation of unstable contractions in idiopathic detrusor overactivity. [67][68][69] Animal studies of bladder strips from guinea pigs 70 and rats 71 indicate that BTX-A inhibits the release of both acetylcholine and ATP, providing a rationale for its possible use in treating patients with idiopathic detrusor overactivity.…”

Section: Effects On Acetylcholine and Atp Releasementioning

confidence: 99%

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

et al. 2008

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SUMMARYBotulinum toxins can effectively and selectively disrupt and modulate neurotransmission in striated muscle. Recently, urologists have become interested in the use of these toxins in patients with detrusor overactivity and other urological disorders. In both striated and smooth muscle, botulinum toxin A (BTX-A) is internalized by presynaptic neurons after binding to an extracellular receptor (ganglioside and presumably synaptic vesicle protein 2C). In the neuronal cytosol, BTX-A disrupts fusion of the acetylcholine-containing vesicle with the neuronal wall by cleaving the SNAP-25 protein in the synaptic fusion complex. The net effect is selective paralysis of the low-grade contractions of the unstable detrusor, while still allowing high-grade contraction that initiates micturition. Additionally, BTX-A seems to have effects on afferent nerve activity by modulating the release of ATP in the urothelium, blocking the release of substance P, calcitonin gene-related peptide and glutamate from afferent nerves, and reducing levels of nerve growth factor. These effects on sensory feedback loops might not only help to explain the mechanism of BTX-A in relieving symptoms of overactive bladder, but also suggest a potential role for BTX-A in the relief of hyperalgesia associated with lower urinary tract disorders.

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Section: Effects On Acetylcholine and Atp Releasementioning

confidence: 99%

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

et al. 2008

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“…This finding confirms previous results from localization studies in animals 17 and humans. 7,8 The data presented here demonstrate that P 2 X 2 receptors are frequently expressed in neurogenic detrusor overactivity. Moreover, we found P 2 X 2 receptor expression in idiopathic detrusor overactivity in 72% of the specimens, confirming previous findings that this receptor subtype is frequently expressed in tissues from overactive detrusors.…”

Section: Discussionmentioning

confidence: 55%

“…7 Moreover, P 2 X receptors play a role in detrusor motor function as well. In patients with idiopathic overactive bladder (OAB), an increased expression of the P 2 X 2 subtype protein 8 and a loss of P 2 X 3 and P 2 X 5 proteins have been described. 9 Thus, it seems that an abnormal expression of P 2 X receptors may lead to a disturbance of the purinergic inhibitory control of the parasympathetic release of acetylcholine.…”

Section: Introductionmentioning

confidence: 99%

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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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“…On the other hand, the proportion of atropine-resistant, nerve-mediated contractions in human bladders increases in several pathological conditions (interstitial cystitis, idiopathic detrusor overactivity, etc. ; Bayliss et al 1999;Sjogren et al 1982;O'Reilly et al 2002). A possible explanation of the different phenotypes of contractions is that in bladders from pathological states, ectonucleotidase enzyme activity is reduced.…”

Section: Introductionmentioning

confidence: 99%

Nicotine interferes with purinergic signaling in smooth muscle cells isolated from urinary bladders of patients with lower urinary tract symptoms

Jenes¹,

Szigeti²,

Ruzsnavszky³

et al. 2014

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Abstract. In patients with outlet obstruction, the contraction of the base is reduced compared to that of healthy individuals, while the contraction of the dome is not affected. Here, we investigated the cellular mechanisms that might be responsible for cholinergic effects blocking non-adrenergic non-cholinergic contractions in the base of the urinary bladder.Smooth muscle cells either from the base or from the dome of human urinary bladders were cultured to determine the contribution of cholinergic and purinergic mechanisms to their Ca 2+ homeostasis.While ATP evoked Ca 2+ transients in all the cells, nicotine and carbachol induced Ca 2+ transients only in 56% and 44% of the cells, respectively. When ATP was administered together with nicotine or carbachol, the amplitudes of the Ca 2+ transients recorded from cells prepared from the base of bladders were significantly smaller (42 ± 6% with nicotine and 56 ± 9% with carbachol) than those evoked by ATP alone. This inhibition was much less apparent in the dome of bladders.The inhibition between the cholinergic and purinergic signaling pathways reported in this work may decrease the strength of the contraction of the base of the urinary bladder in patients with outlet obstruction during voiding.

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P2x Receptors and Their Role in Female Idiopathic Detrusor Instability

Abstract: In patients with idiopathic detrusor instability there is abnormal purinergic transmission in the bladder, which may explain symptoms. This pathway may be a novel target for the pharmacological treatment of overactive bladder.

Cited by 168 publications

References 36 publications

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

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

Nicotine interferes with purinergic signaling in smooth muscle cells isolated from urinary bladders of patients with lower urinary tract symptoms

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