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Published in: International Urology and Nephrology 10/2014

01-10-2014 | Urology - Original Paper

Effects of sensory neuron-specific receptor agonist on bladder function in a rat model of cystitis induced by cyclophosphamide

Authors: Masashi Honda, Naoki Yoshimura, Bunya Kawamoto, Naoto Kobayashi, Katsuya Hikita, Kuniyasu Muraoka, Motoaki Saito, Takehiro Sejima, Michael B. Chancellor, Atsushi Takenaka

Published in: International Urology and Nephrology | Issue 10/2014

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Abstract

Purpose

To investigate the effects of activation of sensory neuron-specific receptors (SNSRs) on cyclophosphamide (CYP) bladder overactivity in rats.

Methods

Female Sprague–Dawley rats (235–258 g) were used. Rats were injected with either CYP (200 mg/kg, intraperitoneally) or saline (control). Continuous cystometrograms (0.04 ml/min) were recorded 48 h after CYP or saline injection under urethane anesthesia. After stable micturition cycles were established, a selective rat SNSR1 agonist, bovine adrenal medulla 8-22 (BAM8-22), was administered intravenously or intrathecally.

Results

Cyclophosphamide treatment-induced higher baseline pressure and shorter intercontraction intervals compared with the control group. Intravenous administration of BAM8-22 at 10, 30 and 100 μg/kg significantly increased intercontraction intervals in the CYP-treated group. Intrathecal administration of BAM8-22 at 0.03, 0.1 and 0.3 μg also significantly increased intercontraction intervals in the CYP-treated group. Intravenous or intrathecal administration of BAM8-22 did not change baseline pressure or maximum voiding pressure in the CYP-treated group.

Conclusions

These findings indicate that activation of SNSRs can suppress CYP-induced bladder overactivity, probably due to suppression of bladder afferent activity.
Literature
1.
go back to reference de Groat WC (1993) Anatomy and physiology of the lower urinary tract. Urol Clin North Am 20:383–401PubMed de Groat WC (1993) Anatomy and physiology of the lower urinary tract. Urol Clin North Am 20:383–401PubMed
2.
go back to reference Vera PL, Nadelhaft I (1992) Afferent and sympathetic innervation of the dome and the base of the urinary bladder of the female rat. Brain Res Bull 29:651–658PubMedCrossRef Vera PL, Nadelhaft I (1992) Afferent and sympathetic innervation of the dome and the base of the urinary bladder of the female rat. Brain Res Bull 29:651–658PubMedCrossRef
3.
go back to reference Maggi CA, Conte B (1990) Effect of urethane anesthesia on the micturition reflex in capsaicin-treated rats. J Auton Nerv Syst 30:247–251PubMedCrossRef Maggi CA, Conte B (1990) Effect of urethane anesthesia on the micturition reflex in capsaicin-treated rats. J Auton Nerv Syst 30:247–251PubMedCrossRef
4.
go back to reference Yoshimura N, Chancellor MB (2002) Current and future pharmacological treatment for overactive bladder. J Urol 168:1897–1913PubMedCrossRef Yoshimura N, Chancellor MB (2002) Current and future pharmacological treatment for overactive bladder. J Urol 168:1897–1913PubMedCrossRef
5.
go back to reference Oyama T, Homan T, Kyotani J, Oka M (2012) Effects of tramadol on pain-related behaviors and bladder overactivity in rodent cystitis models. Eur J Pharmacol 676:75–80PubMedCrossRef Oyama T, Homan T, Kyotani J, Oka M (2012) Effects of tramadol on pain-related behaviors and bladder overactivity in rodent cystitis models. Eur J Pharmacol 676:75–80PubMedCrossRef
6.
go back to reference Yoshikawa S, Oguchi T, Funahashi Y, de Groat WC, Yoshimura N (2012) Glycine transporter type 2 (GlyT2) inhibitor ameliorates bladder overactivity and nociceptive behavior in rats. Eur Urol 62:704–712PubMedCrossRefPubMedCentral Yoshikawa S, Oguchi T, Funahashi Y, de Groat WC, Yoshimura N (2012) Glycine transporter type 2 (GlyT2) inhibitor ameliorates bladder overactivity and nociceptive behavior in rats. Eur Urol 62:704–712PubMedCrossRefPubMedCentral
7.
go back to reference Chuang YC, Tyagi P, Huang CC, Chancellor MB, Yoshimura N (2012) Mechanisms and urodynamic effects of a potent and selective EP4 receptor antagonist, MF191, on cyclophosphamide and prostaglandin E2-induced bladder overactivity in rats. BJU Int 110:1558–1564PubMedCrossRef Chuang YC, Tyagi P, Huang CC, Chancellor MB, Yoshimura N (2012) Mechanisms and urodynamic effects of a potent and selective EP4 receptor antagonist, MF191, on cyclophosphamide and prostaglandin E2-induced bladder overactivity in rats. BJU Int 110:1558–1564PubMedCrossRef
8.
go back to reference Lembo PM, Grazzini E, Groblewski T, O’Donnell D, Roy MO, Zhang J, Hoffert C, Cao J, Schmidt R, Pelletier M, Labarre M, Gosselin M, Fortin Y, Banville D, Shen SH, Ström P, Payza K, Dray A, Walker P, Ahmad S (2002) Proenkephalin a gene products activate a new family of sensory neuron–specific GPCRs. Nat Neurosci 5:201–209PubMedCrossRef Lembo PM, Grazzini E, Groblewski T, O’Donnell D, Roy MO, Zhang J, Hoffert C, Cao J, Schmidt R, Pelletier M, Labarre M, Gosselin M, Fortin Y, Banville D, Shen SH, Ström P, Payza K, Dray A, Walker P, Ahmad S (2002) Proenkephalin a gene products activate a new family of sensory neuron–specific GPCRs. Nat Neurosci 5:201–209PubMedCrossRef
9.
go back to reference Dong X, Han SK, Zylka MJ, Simon MI, Anderson DJ (2001) A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell 106:619–632PubMedCrossRef Dong X, Han SK, Zylka MJ, Simon MI, Anderson DJ (2001) A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell 106:619–632PubMedCrossRef
10.
go back to reference Bender E, Buist A, Jurzak M, Langlois X, Baggerman G, Verhasselt P, Ercken M, Guo HQ, Wintmolders C, Van den Wyngaert I, Van Oers I, Schoofs L, Luyten W (2002) Characterization of an orphan G protein-coupled receptor localized in the dorsal root ganglia reveals adenine as a signaling molecule. Proc Natl Acad Sci USA 99:8573–8578PubMedCrossRefPubMedCentral Bender E, Buist A, Jurzak M, Langlois X, Baggerman G, Verhasselt P, Ercken M, Guo HQ, Wintmolders C, Van den Wyngaert I, Van Oers I, Schoofs L, Luyten W (2002) Characterization of an orphan G protein-coupled receptor localized in the dorsal root ganglia reveals adenine as a signaling molecule. Proc Natl Acad Sci USA 99:8573–8578PubMedCrossRefPubMedCentral
11.
go back to reference Han SK, Dong X, Hwang JI, Zylka MJ, Anderson DJ, Simon MI (2002) Orphan G protein-coupled receptors MrgA1 and MrgC11 are distinctively activated by RF-amide-related peptides through the Galpha q/11 pathway. Proc Natl Acad Sci USA 99:14740–14745PubMedCrossRefPubMedCentral Han SK, Dong X, Hwang JI, Zylka MJ, Anderson DJ, Simon MI (2002) Orphan G protein-coupled receptors MrgA1 and MrgC11 are distinctively activated by RF-amide-related peptides through the Galpha q/11 pathway. Proc Natl Acad Sci USA 99:14740–14745PubMedCrossRefPubMedCentral
12.
go back to reference Zylka MJ, Dong X, Southwell AL, Anderson DJ (2003) Atypical expansion in mice of the sensory neuron-specific Mrg G protein-coupled receptor family. Proc Natl Acad Sci USA 100:10043–10048PubMedCrossRefPubMedCentral Zylka MJ, Dong X, Southwell AL, Anderson DJ (2003) Atypical expansion in mice of the sensory neuron-specific Mrg G protein-coupled receptor family. Proc Natl Acad Sci USA 100:10043–10048PubMedCrossRefPubMedCentral
13.
go back to reference Grazzini E, Puma C, Roy MO, Yu XH, O’Donnell D, Schmidt R, Dautrey S, Ducharme J, Perkins M, Panetta R, Laird JM, Ahmad S, Lembo PM (2004) Sensory neuron-specific receptor activation elicits central and peripheral nociceptive effects in rats. Proc Natl Acad Sci USA 101:7175–7180PubMedCrossRefPubMedCentral Grazzini E, Puma C, Roy MO, Yu XH, O’Donnell D, Schmidt R, Dautrey S, Ducharme J, Perkins M, Panetta R, Laird JM, Ahmad S, Lembo PM (2004) Sensory neuron-specific receptor activation elicits central and peripheral nociceptive effects in rats. Proc Natl Acad Sci USA 101:7175–7180PubMedCrossRefPubMedCentral
14.
go back to reference Chen T, Cai Q, Hong Y (2006) Intrathecal sensory neuron-specific receptor agonists bovine adrenal medulla 8-22 and (Tyr6)-gamma2-MSH-6-12 inhibit formalin-evoked nociception and neuronal Fos-like immunoreactivity in the spinal cord of the rat. Neuroscience 141:965–975PubMedCrossRef Chen T, Cai Q, Hong Y (2006) Intrathecal sensory neuron-specific receptor agonists bovine adrenal medulla 8-22 and (Tyr6)-gamma2-MSH-6-12 inhibit formalin-evoked nociception and neuronal Fos-like immunoreactivity in the spinal cord of the rat. Neuroscience 141:965–975PubMedCrossRef
15.
go back to reference Honda M, Takenaka A, Inoue S, Chancellor MB, Yoshimura N (2011) Sensory neurone-specific receptor-mediated regulation of micturition reflex in urethane-anaesthetized rats. BJU Int 109:628–633PubMedCrossRefPubMedCentral Honda M, Takenaka A, Inoue S, Chancellor MB, Yoshimura N (2011) Sensory neurone-specific receptor-mediated regulation of micturition reflex in urethane-anaesthetized rats. BJU Int 109:628–633PubMedCrossRefPubMedCentral
16.
go back to reference Dores RM, Mcdonald LK, Steveson TC, Sei CA (1990) The molecular evolution of neuropeptides: prospects for the ‘90s. Brain Behav Evol 36:80–99PubMedCrossRef Dores RM, Mcdonald LK, Steveson TC, Sei CA (1990) The molecular evolution of neuropeptides: prospects for the ‘90s. Brain Behav Evol 36:80–99PubMedCrossRef
17.
go back to reference Khachaturian H, Lewis ME, Watson SJ (1983) Colocalization of proenkephalin peptides in rat brain neurons. Brain Res 279:369–373PubMedCrossRef Khachaturian H, Lewis ME, Watson SJ (1983) Colocalization of proenkephalin peptides in rat brain neurons. Brain Res 279:369–373PubMedCrossRef
18.
go back to reference Pittius CW, Seizinger BR, Pasi A, Mehraein P, Herz A (1984) Distribution and characterization of opioid peptides derived from proenkephalin A in human and rat central nervous system. Brain Res 304:127–136PubMedCrossRef Pittius CW, Seizinger BR, Pasi A, Mehraein P, Herz A (1984) Distribution and characterization of opioid peptides derived from proenkephalin A in human and rat central nervous system. Brain Res 304:127–136PubMedCrossRef
19.
go back to reference Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824PubMedCrossRef Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824PubMedCrossRef
20.
go back to reference Avelino A, Cruz F (2006) TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications. Naunyn Schmiedebergs Arch Pharmacol 373:287–299PubMedCrossRef Avelino A, Cruz F (2006) TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications. Naunyn Schmiedebergs Arch Pharmacol 373:287–299PubMedCrossRef
21.
go back to reference Lanteri-Minet M, Bon K, de Pommery J, Michiels JF, Menétrey D (1995) Cyclophosphamide cystitis as a model of visceral pain in rats: model elaboration and spinal structures involved as revealed by the expression of c-Fos and Krox-24 proteins. Exp Brain Res 105:220–232PubMedCrossRef Lanteri-Minet M, Bon K, de Pommery J, Michiels JF, Menétrey D (1995) Cyclophosphamide cystitis as a model of visceral pain in rats: model elaboration and spinal structures involved as revealed by the expression of c-Fos and Krox-24 proteins. Exp Brain Res 105:220–232PubMedCrossRef
22.
go back to reference Dinis P, Charrua A, Avelino A, Yaqoob M, Bevan S, Nagy I, Cruz F (2004) Anandamide-evoked activation of vanilloid receptor 1 contributes to the development of hyperreflexia and nociceptive transmission to spinal dorsal horn neurons in cystitis. J Neurosci 24:11253–11263PubMedCrossRef Dinis P, Charrua A, Avelino A, Yaqoob M, Bevan S, Nagy I, Cruz F (2004) Anandamide-evoked activation of vanilloid receptor 1 contributes to the development of hyperreflexia and nociceptive transmission to spinal dorsal horn neurons in cystitis. J Neurosci 24:11253–11263PubMedCrossRef
23.
go back to reference Szallasi A, Nilsson S, Farkas-Szallasi T, Blunberg PM, Hökfelt T, Lundberg JM (1995) Vanilloid (capsaicin) receptors in the rat: distribution in the brain, regional differences in the spinal cord, axonal transport to the periphery, and depletion by systemic vanilloid treatment. Brain Res 703:175–183PubMedCrossRef Szallasi A, Nilsson S, Farkas-Szallasi T, Blunberg PM, Hökfelt T, Lundberg JM (1995) Vanilloid (capsaicin) receptors in the rat: distribution in the brain, regional differences in the spinal cord, axonal transport to the periphery, and depletion by systemic vanilloid treatment. Brain Res 703:175–183PubMedCrossRef
24.
go back to reference Vizzard MA (2000) Alterations in spinal cord Fos protein expression induced by bladder stimulation following cystitis. Am J Physiol Regul Integr Comp Physiol 278:R1027–R1039PubMed Vizzard MA (2000) Alterations in spinal cord Fos protein expression induced by bladder stimulation following cystitis. Am J Physiol Regul Integr Comp Physiol 278:R1027–R1039PubMed
25.
go back to reference Miyazato M, Sasatomi K, Hiragata S, Sugaya K, Chancellor MB, de Groat WC, Yoshimura N (2008) GABA receptor activation in the spinal cord decreases detrusor overactivity in spinal cord injured rats. J Urol 179:1178–1183PubMedCrossRefPubMedCentral Miyazato M, Sasatomi K, Hiragata S, Sugaya K, Chancellor MB, de Groat WC, Yoshimura N (2008) GABA receptor activation in the spinal cord decreases detrusor overactivity in spinal cord injured rats. J Urol 179:1178–1183PubMedCrossRefPubMedCentral
26.
go back to reference Rice AS, McMahon SB (1994) Pre-emptive intrathecal administration of an NMDA receptor antagonist (AP-5) prevents hyper-reflexia in a model of persistent vesical pain. Pain 57:335–340PubMedCrossRef Rice AS, McMahon SB (1994) Pre-emptive intrathecal administration of an NMDA receptor antagonist (AP-5) prevents hyper-reflexia in a model of persistent vesical pain. Pain 57:335–340PubMedCrossRef
Metadata
Title
Effects of sensory neuron-specific receptor agonist on bladder function in a rat model of cystitis induced by cyclophosphamide
Authors
Masashi Honda
Naoki Yoshimura
Bunya Kawamoto
Naoto Kobayashi
Katsuya Hikita
Kuniyasu Muraoka
Motoaki Saito
Takehiro Sejima
Michael B. Chancellor
Atsushi Takenaka
Publication date
01-10-2014
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 10/2014
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-014-0734-x

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