Altered muscarinic receptor subtype expression and functional responses in cyclophosphamide induced cystitis in rats

Giglio, Daniel; Ryberg, Anders T.; To, King; Delbro, Dick; Tobin, Gunnar

doi:10.1016/j.autneu.2005.07.005

Cited by 86 publications

(133 citation statements)

References 26 publications

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“…In the current study, there was a marked decrease in the density of muscarinic and P2X receptors in the bladders of CYPtreated rats, as shown by a significant reduction in the B max for specific binding of [ 3 H]NMS and [ 3 H]abMeATP. These results revealed a down-regulation in pharmacologically relevant muscarinic and purinergic receptors in the bladders of rats with cystitis, which is consistent with pharmacological subsensitivity to cholinergic and purinergic agonists in CYP-treated bladders (22,23). The down-regulation of pharmacological receptors in CYP-treated bladders may reflect a compensatory mechanism, possibly due to the increased stimulation of receptors by acetylcholine or ATP (23 -26).…”

Section: Discussionsupporting

confidence: 61%

Beneficial Effects of Gosha-jinki-gan and Green Tea Extract in Rats With Chemical Cystitis

Nasrin¹,

Osano²,

Ito³

et al. 2013

J Pharmacol Sci

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Abstract. The aim of this study was to characterize pharmacological effects of gosha-jinki-gan (GJG) and green tea extract (GTE), on urodynamic parameters, bladder receptors, and urinary cytokines in rats with cyclophosphamide (CYP)-induced cystitis. Urodynamic parameters in CYPtreated rats were measured using the cystometric method. Muscarinic and purinergic receptors in rat tissues were measured by radioreceptor assays. Urinary cytokine levels were measured with ELISA kits. GJG and GTE were orally administered to rats once a day for 7 days. The GJG treatment significantly ameliorated changes in urodynamic parameters in CYP-treated rats. Similar treatment with GTE slightly attenuated changes in urodynamic parameters. The maximal number of binding sites for [ H]NMS and [3 H]ab-MeATP in the bladder was significantly lower in CYPtreated rats than in sham rats. Such a reduction in receptor density was significantly attenuated by the GJG treatment. GTE treatment also significantly attenuated the down-regulation of muscarinic receptors, but not P2X receptors in bladders of rats with CYP-induced cystitis. The elevation in urinary cytokine levels in CYP-treated rats was effectively attenuated by GJG treatment. The elevation in cytokine levels in CYP-treated rats was alleviated by GTE treatment. In conclusion, GJG may be a pharmacologically useful plant extract for cystitis.

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Section: Discussionsupporting

confidence: 61%

Beneficial Effects of Gosha-jinki-gan and Green Tea Extract in Rats With Chemical Cystitis

Nasrin¹,

Osano²,

Ito³

et al. 2013

J Pharmacol Sci

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“…Buffington et al [11] showed that acetylcholine release was not altered following EFS in bladder tissue strips of cats with feline interstitial cystitis. Giglio et al [12] further demonstrated that in cyclophosphamide-treated rats the expression and distribution of M2 and M3 receptor subtypes in the urothelium and smooth muscle layer were not changed when compared with control animals. However, they found that contractile responses to carbachol were significantly reduced in cyclophosphamide-treated tissues, possibly due to harmful effects of cyclophosphamide on smooth muscle contractility.…”

Section: Discussionmentioning

confidence: 96%

Prophylactic Role of Oral <i>L</i>-Arginine on Histological and Contractile Changes in a Rat Chronic Bladder Injury Model

Özgür¹,

Önol²,

Ercan³

et al. 2008

Urol Int

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Introduction: The effect of L-arginine on bladder tissue structure and function in a rat bladder injury model were investigated. Methods: 24 male Sprague-Dawley rats were used. The control group received a regular diet. The L-arginine group received oral L-arginine (1 g/day). The protamine sulfate (PS) group received intravesical PS every 48 h (0.5 ml, 5 mg/ml). L-Arginine was administered to the PS+L-arginine group in addition to PS. At the end of 1 week, bladder tissues were processed for histological and functional studies. Results: The PS group revealed urothelial damage with glycosaminoglycan layer irregularity and mast cell infiltration which was not evident in the PS+L-arginine group. 120 mM potassium and electrical field stimulation (EFS)-induced contractions in the PS group were significantly lower than in other groups, whereas carbachol-induced contractions were not significantly different. Relaxation responses of precontracted strips to EFS and isoproterenol did not reveal a significant decrease in the PS group, whereas L-arginine significantly enhanced these responses in PS-treated animals. Conclusions: Intravesical PS causes urothelial damage and inflammation that is associated with significant changes in rat bladder tissue contractility. Oral L-arginine treatment is found to prevent these histological and contractile alterations. Our findings may indicate the nitric oxide-cGMP pathway as a possible therapeutic target in various bladder diseases associated with urothelial damage.

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“…23 Bradykinin receptor B 1 and cannabinoid receptors CB1 and CB2 are involved in the regulation of pain and inflammatory responses in human bladder. 59,60 We detected a significant (P Ͻ 0.05) up-regulation of the inflammation-induced bradykinin receptor B 1 and cannabinoid CB1 receptors.…”

Section: Discussionmentioning

confidence: 99%

“…20 Such changes are indicative of the pathophysiological processes taking place during the progression of a disease; therefore some of the causative factors of BPS/IC might be elucidated by uncovering a link between the expression of proteins, mediating neurogenic inflammation, bladder contractility and epithelial permeability. Although there are several studies examining gene expression changes during experimentally induced cystitis in animals, [21][22][23][24][25] human data are scarce. In human BPS patients, the molecular markers for bladder permeability and proteoglycan core proteins have been shown to be down-regulated, 26,27 and there was an increased permeability and decreased tight junction formation of bladder epithelial cell monolayers grown from biopsies in patients with BPS/IC, as compared with cells from normal controls.…”

mentioning

confidence: 99%

MicroRNAs May Mediate the Down-Regulation of Neurokinin-1 Receptor in Chronic Bladder Pain Syndrome

Freire

Burkhard

Kessler

et al. 2010

The American Journal of Pathology

101

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Bladder pain syndrome (BPS) is a clinical syndrome of pelvic pain and urinary urgency-frequency in the absence of a specific cause. Investigating the expression levels of genes involved in the regulation of epithelial permeability , bladder contractility , and inflammation , we show that neurokinin (NK)1 and NK2 tachykinin receptors were significantly down-regulated in BPS patients. Tight junction proteins zona occludens-1 , junctional adherins molecule -1 , and occludin were similarly down-regulated , implicating increased urothelial permeability , whereas bradykinin B 1 receptor , cannabinoid receptor CB1 and muscarinic receptors M3-M5 were up-regulated. Using cellbased models , we show that prolonged exposure of NK1R to substance P caused a decrease of NK1R mRNA levels and a concomitant increase of regulatory micro(mi)RNAs miR-449b and miR-500. In the biopsies of BPS patients , the same miRNAs were significantly increased , suggesting that BPS promotes an attenuation of NK1R synthesis via activation of specific miRNAs. We confirm this hypothesis by identifying 31 differentially expressed miRNAs in BPS patients and demonstrate a direct correlation between miR-449b , miR-500 , miR-328 , and miR-320 and a down-regulation of NK1R mRNA and/or protein levels. Our findings further the knowledge of the molecular mechanisms of BPS , and have relevance for other clinical conditions involving the NK1 receptor. (Am J

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Altered muscarinic receptor subtype expression and functional responses in cyclophosphamide induced cystitis in rats

Cited by 86 publications

References 26 publications

Beneficial Effects of Gosha-jinki-gan and Green Tea Extract in Rats With Chemical Cystitis

Beneficial Effects of Gosha-jinki-gan and Green Tea Extract in Rats With Chemical Cystitis

Prophylactic Role of Oral <i>L</i>-Arginine on Histological and Contractile Changes in a Rat Chronic Bladder Injury Model

MicroRNAs May Mediate the Down-Regulation of Neurokinin-1 Receptor in Chronic Bladder Pain Syndrome

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