방광 내 아데노신 트리포스페이트 주입으로 유발된 백서방광의 배뇨근과활동성의 특징 = Characteristics of Detrusor Overactivity Induced by Intravesical Instillation of Adenosine 5'-Triphosphate

다국어 초록 (Multilingual Abstract)

Purpose: The bladder urothelium releases adenosine 5'-triphosphate(ATP) with mechanical stretch, which increases in a pathologic state such as a neurogenic bladder. We investigated the characteristics of detrusor overactivity induced by the intravesical instillation of ATP.
Materials and Methods: Under urethane anesthesia, cystometry was performed on female Sprague-Dawley rats. After pretreatment with protamine sulfate(PS, 10mg/ml), ATP(60mM, pH 6.0) was continuously infused intravesically. The effects of intravenous injection of pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid(PPADS) on ATP-induced detrusor overactivity were studied. Changes in cystometric parameters including parameters of each voiding phase, including bladder pressure increase rate(slope; Ph1slope), maximal bladder pressure(Ph1MBP, Ph2MBP, Ph3MBP), mean bladder pressure(Ph2meanBP) and variation of intraluminal pressure high-frequency oscillations(IPHFOs) were analysed.
Results: With the intravesical instillation of ATP after PS pretreatment, the intercontraction interval(ICI) decreased significantly(544.2±167.2s vs 222.3±170.8s, p=0.001), maximal voiding pressure(MVP) decreased significantly(31.3±4.7cmH2O vs 25±2.9cmH2O, p=0.001), and pressure threshold (PT) decreased significantly(4.0±1.3cmH2O vs 1.4±0.8cmH2O, p=0.001). Changes in the ICI, MVP & PT induced by intravesical instillation of ATP were reversed by intravenous injection of PPADS. Ph1slope, Ph1MBP, Ph2MBP, Ph2meanBP and Ph3MBP were decreased, but IPHFOs were not affected by intravesical application of ATP.
Conclusions: Intravesical instillation of ATP in female rats induced detrusor overactivity, which may be mediated by acting on the urine storage phase. (Korean J Urol 2008;49:424-431)

다국어 초록 (Multilingual Abstract)

Purpose: The bladder urothelium releases adenosine 5'-triphosphate(ATP) with mechanical stretch, which increases in a pathologic state such as a neurogenic bladder. We investigated the characteristics of detrusor overactivity induced by the intravesical instillation of ATP.
Materials and Methods: Under urethane anesthesia, cystometry was performed on female Sprague-Dawley rats. After pretreatment with protamine sulfate(PS, 10mg/ml), ATP(60mM, pH 6.0) was continuously infused intravesically. The effects of intravenous injection of pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid(PPADS) on ATP-induced detrusor overactivity were studied. Changes in cystometric parameters including parameters of each voiding phase, including bladder pressure increase rate(slope; Ph1slope), maximal bladder pressure(Ph1MBP, Ph2MBP, Ph3MBP), mean bladder pressure(Ph2meanBP) and variation of intraluminal pressure high-frequency oscillations(IPHFOs) were analysed.
Results: With the intravesical instillation of ATP after PS pretreatment, the intercontraction interval(ICI) decreased significantly(544.2±167.2s vs 222.3±170.8s, p=0.001), maximal voiding pressure(MVP) decreased significantly(31.3±4.7cmH2O vs 25±2.9cmH2O, p=0.001), and pressure threshold (PT) decreased significantly(4.0±1.3cmH2O vs 1.4±0.8cmH2O, p=0.001). Changes in the ICI, MVP & PT induced by intravesical instillation of ATP were reversed by intravenous injection of PPADS. Ph1slope, Ph1MBP, Ph2MBP, Ph2meanBP and Ph3MBP were decreased, but IPHFOs were not affected by intravesical application of ATP.
Conclusions: Intravesical instillation of ATP in female rats induced detrusor overactivity, which may be mediated by acting on the urine storage phase. (Korean J Urol 2008;49:424-431)

참고문헌 (Reference)

1 Streng T, "Transmitters contributing to the voiding contraction in female rats" 94 : 910-914, 2004

2 de Groat WC, "The urothelium in overactive bladder: passive bystander or active participant?" 64(6 suppl 1) : 7-11, 2004

3 Cetinel S, "The ameliorating effect of melatonin on protamine sulfate induced bladder injury and its relationship to interstitial cystitis" 169 : 1564-1658, 2003

4 Salas NA, "Receptor activated bladder and spinal ATP release in neurally intact and chronic spinal cord injured rats" 50 : 345-350, 2007

5 Andersson KE, "Pharmacologic perspective on the physiology of the lower urinary tract" 60(5 Suppl 1) : 13-20, 2002

6 Ziganshin AU, "PPADS selectively antagonizes P2X- purinoceptor-mediated responses in the rabbit urinary bladder" 110 : 1491-1495, 1993

7 Vlaskovska M, "P2X3 knock-out mice reveal a major sensory role for urothelially released ATP" 21 : 5670-5677, 2001

8 Maggi CA, "Nervous control of the urogenital system" Harwood Academic Publishers 227-289, 1993

9 Kim JC, "Muscarinic and purinergic receptor expression in the urothelium of rats with detrusor overactivity induced by bladder outlet obstruction" 101 : 371-375, 2008

10 Gillespie JI, "Modulation of autonomous contractile activity in the isolated whole bladder of the guinea pig" 93 : 393-400, 2004

11 Ruggieri MR Sr, "Mechanisms of disease: role of purinergic signaling in the pathophysiology of bladder dysfunction" 3 : 206-215, 2006

12 Masuda H, "Local effects of antimuscarinics" 33 : 511-518, 2006

13 Kim Y, "Intravesical instillation of human urine after oral administration of trospium, tolterodine and oxybutynin in a rat model of detrusor overactivity" 97 : 400-403, 2006

14 Pandita RK, "Intravesical adenosine triphosphate stimulates the micturition reflex in awake, freely moving rats" 168 : 1230-1234, 2002

15 Zhang X, "Effects of resiniferatoxin desensitization of capsaicin-sensitive afferents on detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP in conscious rats" 367 : 473-479, 2003

16 Nishiguchi J, "Effects of isolectin B4-conjugated saporin, a targeting cytotoxin, on bladder overactivity induced by bladder irritation" 20 : 474-482, 2004

17 Ozawa H, "Effect of intravesical nitric oxide therapy on cyclophosphamide-induced cystitis" 162 : 2211-2216, 1999

18 Atiemo H, "Effect of botulinum toxin on detrusor overactivity induced by intravesical adenosine triphosphate and capsaicin in a rat model" 65 : 622-626, 2005

19 Nishiguchi J, "Detrusor overactivity induced by intravesical application of adenosine 5'-triphosphate under different delivery conditions in rats" 66 : 1332-1337, 2005

20 Yiangou Y, "Capsaicin receptor VR1 and ATP-gated ion channel P2X3 in human urinary bladder" 87 : 774-779, 2001

21 Stein PC, "Bladder injury model induced in rats by exposure to protamine sulfate followed by bacterial endotoxin" 155 : 1133-1138, 1996

22 Dang K, "Bielefeldt K, Gebhart GF. Cyclophosphamide-induced bladder inflammation sensitizes and enhances P2X receptor function in rat bladder sensory neurons" 99 : 49-59, 2008

23 Sun Y, "Augmented stretch activated adenosine triphosphate release from bladder uroepithelial cells in patients with interstitial cystitis" 166 : 1951-1956, 2001

24 Zeybek A, "Aqueous garlic extract inhibits protamine sulfate-induced bladder damage" 76 : 173-179, 2006

25 Hoheisel U, "Acidic pH and capsaicin activate mechanosensitive group IV muscle receptors in the rat" 110 : 149-157, 2004

26 Ifshin MS, "Acid pH and weak acids induce Na-Cl cotransport in the rabbit urinary bladder" 76 : 151-164, 1983

27 Slobodov G, "Abnormal expression of molecular markers for bladder impermeability and differentiation in the urothelium of patients with interstitial cystitis" 171 : 1554-1558, 2004

28 Ferguson DR, "ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes-a possible sensory mechanism?" 505 : 503-511, 1997

29 Grycova L, "ATP binding site on the C-terminus of the vanilloid receptor" 465 : 389-398, 2007

30 de Groat WC, "A neurologic basis for the overactive bladder" 50(6A suppl) : 36-52, 1997