Purinergic sensory neurotransmission in the urinary bladder: an <i>in vitro</i> study in the rat

Namasivayam, Siva; Eardley, Ian; Morrison, J.

doi:10.1046/j.1464-410x.1999.00310.x

Cited by 96 publications

(86 citation statements)

References 25 publications

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“…Neocuproine could modulate purinergic mechanisms at several sites in the bladder including postjunctional purinergic receptors in the smooth muscle, as well as purinergic receptors in afferent nerves and urothelial cells (Namasivayam et al, 1999;de Groat and Yoshimura, 2001;Vlaskovska et al, 2001;Andersson, 2002;Rong et al, 2002;Birder et al, 2003). The initial component of the neurally evoked contractions of detrusor smooth muscle that persisted in the presence of atropine and guanethidine was suppressed by suramin, a P2X purinergic receptor antagonist as reported by other investigators (Hoyle et al, 1990;Calvert et al, 2001;Burnstock, 2002;Benko et al, 2003).…”

Section: Discussionmentioning

confidence: 52%

“…ATP released from parasympathetic postganglionic nerves can activate postjunctional P2X receptors to elicit atropine resistant contractions of the bladder smooth muscle (Hoyle et al, 1989;Ruggieri et al, 1990;Acevedo et al, 1992;Burnstock, 2002). On the other hand, ATP released from urothelial cells can act on P2X 3 or P2X 2/3 excitatory receptors on subepithelial afferent nerves or on urothelial purinergic receptors to modulate sensory mechanisms in the bladder (Namasivayam et al, 1999;de Groat and Yoshimura, 2001;Vlaskovska et al, 2001;Andersson, 2002;Rong et al, 2002;Birder et al, 2003). Intravesical administration of ATP induces a facilitation of voiding, which is suppressed by P2X receptor antagonists (Andersson, 2002), whereas P2X 3 receptor-null mice exhibit hypoactive voiding, suggesting that purinergic excitatory mechanisms are essential for normal bladder function (Cockayne et al, 2000).…”

mentioning

confidence: 99%

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Effect of Neocuproine, a Copper(I) Chelator, on Rat Bladder Function

Göçmen

Giesselman²,

Groat³

2004

J Pharmacol Exp Ther

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The effects of a specific copper(I)-chelator, neocuproine (NC), and a selective copper(II)-chelator, cuprizone, on nonadrenergic-noncholinergic transmitter mechanisms in the rat urinary bladder were studied by measuring nerve-evoked contractions of bladder strips and voiding function under urethane anesthesia. After blocking cholinergic and adrenergic transmission with atropine and guanethidine, electrical field stimulation induced bimodal contractions of bladder strips. An initial, transient contraction that was blocked by the purinergic antagonist, suramin, was significantly enhanced by NC (20 and 200 M applied sequentially) but not affected by cuprizone. The facilitating effect, which was blocked by suramin and reversible after washout of the drug, did not occur following administration of neocuproine-copper(I) complex (NC-Cu). NC (20 M) significantly increased the second, more sustained contraction, whereas 200 M decreased this response. These effects of NC on the sustained contractions were not elicited by NC-Cu and not blocked by suramin. The nitric oxide synthase inhibitor, L-nitroarginine, did not alter the responses to NC. NC (20 M) elicited a marked increase in basal tone of the strips. This effect was less prominent after the second application of 200 M NC or with NC-Cu treatment or in the presence of suramin. In anesthetized rats, during continuous infusion cystometry, intravesical infusion of 50 M NC but not NC-Cu or cuprizone significantly decreased the intercontraction interval (ICI) without changing contraction amplitude. The ICI returned to normal after washout of NC. Suramin blocked this effect. These results indicate that NC enhances bladder activity by facilitating purinergic excitatory responses and that copper(I)-sensitive mechanisms tonically inhibit purinergic transmission in the bladder.

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Section: Discussionmentioning

confidence: 52%

mentioning

confidence: 99%

Effect of Neocuproine, a Copper(I) Chelator, on Rat Bladder Function

Göçmen

Giesselman²,

Groat³

2004

J Pharmacol Exp Ther

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“…Prolonged exposure to a desensitising concentration of α,β-meATP significantly reduced the activity of mechanosensitive pelvic nerve afferents in an in vitro model of rat urinary bladder [513]. Later, it was shown that mice lacking the P2X3 receptor exhibited reduced inflammatory pain and marked urinary bladder hyporeflexia with reduced voiding frequency and increased voiding volume, suggesting that P2X3 receptors are involved in mechanosensory transduction underlying both inflammatory pain and hyperreflexia and a role in physiological voiding reflexes was also suggested [158].…”

Section: Afferent Pathways In Bladdermentioning

confidence: 91%

“…Magnesium-dependent adenosine triphosphatase (Mg 2+ -ATPase) as well as 5′-nucleotidase and alkaline phosphatase were identified in the epithelial cells of the rat urinary bladder [756], perhaps functioning to degrade the ATP released from uroepithelial cells [237, 288, 379] during purinergic mechanosensory transduction [104,513]. A recent study using RT-PCR has shown that eight members of the ectonucleoside triphosphate diphosphohydrolase (NTPD) family as well as 5′-nucleotidase are expressed in mouse bladder [750].…”

Section: Ectoenzymatic Breakdown Of Atpmentioning

confidence: 99%

Purinergic signalling in the urinary tract in health and disease

Burnstock

2013

Purinergic Signalling

142

149

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Purinergic signalling is involved in a number of physiological and pathophysiological activities in the lower urinary tract. In the bladder of laboratory animals there is parasympathetic excitatory cotransmission with the purinergic and cholinergic components being approximately equal, acting via P2X1 and muscarinic receptors, respectively. Purinergic mechanosensory transduction occurs where ATP, released from urothelial cells during distension of bladder and ureter, acts on P2X3 and P2X2/3 receptors on suburothelial sensory nerves to initiate the voiding reflex, via low threshold fibres, and nociception, via high threshold fibres. In human bladder t h e p u r i n e rg i c c o m p o n e n t o f p a r a s y m p a t h e t i c cotransmission is less than 3 %, but in pathological conditions, such as interstitial cystitis, obstructed and neuropathic bladder, the purinergic component is increased to 40 %. Other pathological conditions of the bladder have been shown to involve purinoceptor-mediated activities, including multiple sclerosis, ischaemia, diabetes, cancer and bacterial infections. In the ureter, P2X7 receptors have been implicated in inflammation and fibrosis. Purinergic therapeutic strategies are being explored that hopefully will be developed and bring benefit and relief to many patients with urinary tract disorders.

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“…As discussed previously, ATP is released from the urothelium in response to bladder distension (99,291,293), and these findings can be mimicked in isolated urothelial cell cultures (37, 268). Studies using isolated bladder-pelvic nerve preparations from rats (214) or mice (244,291) have shown that distension also leads to increased afferent nerve activity. Such activity can be mimicked by ATP and/or ␣,␤-MeATP, and intravesical instilla-tion of these drugs can also produce bladder overactivity in conscious rats, sensitive to blockade with TNP-ATP (226).…”

Section: G P2x3-receptor Antagonistsmentioning

confidence: 99%

Urothelial Signaling

Birder

Andersson

2013

Physiological Reviews

399

362

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The urothelium, which lines the inner surface of the renal pelvis, the ureters, and the urinary bladder, not only forms a high-resistance barrier to ion, solute and water flux, and pathogens, but also functions as an integral part of a sensory web which receives, amplifies, and transmits information about its external milieu. Urothelial cells have the ability to sense changes in their extracellular environment, and respond to chemical, mechanical and thermal stimuli by releasing various factors such as ATP, nitric oxide, and acetylcholine. They express a variety of receptors and ion channels, including P2X3 purinergic receptors, nicotinic and muscarinic receptors, and TRP channels, which all have been implicated in urothelial-neuronal interactions, and involved in signals that via components in the underlying lamina propria, such as interstitial cells, can be amplified and conveyed to nerves, detrusor muscle cells, and ultimately the central nervous system. The specialized anatomy of the urothelium and underlying structures, and the possible communication mechanisms from urothelial cells to various cell types within the bladder wall are described. Changes in the urothelium/ lamina propria ("mucosa") produced by different bladder disorders are discussed, as well as the mucosa as a target for therapeutic interventions.

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Purinergic sensory neurotransmission in the urinary bladder: an in vitro study in the rat

Abstract: These findings are consistent with the notion that ATP is released endogenously during bladder distension in the rat and is involved significantly in the activation of pelvic nerve afferents arising from the rat urinary bladder.

Cited by 96 publications

References 25 publications

Effect of Neocuproine, a Copper(I) Chelator, on Rat Bladder Function

Effect of Neocuproine, a Copper(I) Chelator, on Rat Bladder Function

Purinergic signalling in the urinary tract in health and disease

Urothelial Signaling

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