Pharmacological analysis of the local and reflex responses to bradykinin on rat urinary bladder motility <i>in vivo</i>

Lecci, Alessandro; Giuliani, Sandro; Meini, Stefania; Maggi, Carlo Alberto

doi:10.1111/j.1476-5381.1995.tb17196.x

Cited by 28 publications

(24 citation statements)

References 42 publications

(47 reference statements)

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“…It also enhanced the response to neuronally mediated bladder contractions. These findings agree with previous evidence that bradykinin acts by sensitizing the primary afferent nerves either through release of sensory neuropeptides from nerve terminals (Marceau et al, 1980;Maggi et al, 1989) or by direct stimulation of bladder afferent nerves (Lecci et al, 1995). It is therefore reasonable to suggest that bradykinin potentiation of neuronally mediated bladder contraction seen in this model is due to the sensitization of intramural nerves and could thus mimic the pathophysiological process involved in chronic inflammation.…”

supporting

confidence: 81%

The Use of the Isolated Mouse Whole Bladder for Investigating Bladder Overactivity

Fabiyi

Brading

2006

J Pharmacol Exp Ther

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The isolated mouse whole bladder was used to study in vitro bladder overactivity evoked by intramural nerve sensitization with bradykinin, mimicking neurogenic bladder overactivity secondary to bladder inflammation. Intravesical pressure responses to intramural electrical stimulation of intramural nerves were measured under isovolumetric condition. Validation showed that carbachol produced a dose-response curve closely mirroring that observed in the isolated muscle strips and demonstrated the dual nature of electrically evoked neurotransmission, consisting of a cholinergic component largely mediated by M 3 receptors and a purinergic component mediated by P2X receptors. ATP generated a biphasic dose-response curve, suggesting that the P2X receptors may be heterogeneous in distribution. Characterization of bradykinin receptors showed bradykinin to be extremely potent in exciting the bladder, producing a dose-response curve with an EC 50 of 90 nM, and bradykinin also enhanced electrically evoked bladder contractions. These effects were inhibited by the B 2 receptor antagonist HOE 140 (D-Arg 0 -Arg

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confidence: 81%

The Use of the Isolated Mouse Whole Bladder for Investigating Bladder Overactivity

Fabiyi

Brading

2006

J Pharmacol Exp Ther

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“…In anaesthetized rats, BK evokes the micturiction reflex by activating capsaicin-sensitive sensory neurons (Lecci et al, 1995), and participates in the genesis of detrusor overactivity in the cyclophosphamide-induced cystitis (Maggi et al, 1993). In the rat isolated urinary bladder, prostanoids seem to be largely responsible for BK-induced contractions (Marceau et al, 1980;Pinna et al, 1992;Meini et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Characterization of kinin receptors in human cultured detrusor smooth muscle cells

Bellucci¹,

Cucchi²,

Santicioli³

et al. 2007

British J Pharmacology

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Background and purpose: Kinins have an important role in inflammatory cystitis and in animal pathophysiological models, by acting on epithelium, fibroblasts, sensory innervation and smooth muscle. The aim of this study was to characterize the receptors responsible for direct motor responses induced by kinins on human detrusor. ]-Lys-BK was 10% of BK). BK also induced prostaglandin E 2 release (EC 50 2.3 nM), whereas no response was detected with the B 1 receptor agonist. The incubation of detrusor smooth muscle cells with interleukin 1b (IL-1b) or tumour necrosis factor-a (TNFa) (10 ng ml À1 ) induced a time-dependent increase in radioligand-specific binding, which was greater for the B 1 than for the B 2 receptor. Conclusions and Implications: Human detrusor smooth muscle cells in culture retain kinin receptors, and represent a suitable model to investigate the mechanisms and changes that occur under chronic inflammatory conditions.

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“…6,7,9) For example, stimulation of the bradykinin B2 receptor produces detrusor muscle contraction 6) and evokes bladder hyperreflexia. 6,7) In this study, we also observed that bradykinin contracts the urinary bladders isolated from control and CYP-treated rats. The amplitude of bradykinin-induced contractions was not significantly different between the control and CYP-treated groups.…”

Section: Discussionmentioning

confidence: 99%

“…Bradykinin, a metabolite of the kallikrein-kinin system, has multiple actions in urinary bladders, including the ability to contract the detrusor smooth muscle, 6) stimulate sensory nerves 6,7) and evoke the release of cyclooxygenase (COX) products. 8) Also, bradykinin might play a key role in the pathogenesis of experimental cystitis 9) and activation of the kallikrein-kinin system in urinary bladders of patients with interstitial cystitis has been reported.…”

mentioning

confidence: 99%

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Involvement of Bradykinin in Trypsin-Induced Urinary Bladder Contraction in Cyclophosphamide-Treated Rats

Shimizu

Nakahara

Tsuda

et al. 2011

Biological & Pharmaceutical Bulletin

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We have previously demonstrated that both trypsin and the PAR-2 activating peptide (SLIGRL-NH 2 ) contract isolated rat urinary bladders by the activation of urothelium PARs and the subsequent release of prostaglandins.3) Furthermore, we found that contractions induced by PAR-2 agonists could be partly mediated through stimulation of capsaicin-sensitive sensory nerves.4) The PAR-2-mediated responses were enhanced after the induction of cystitis with cyclophosphamide (CYP).5) These findings suggested that PAR-2 plays a role in regulating bladder contractility under physiological and pathological conditions. Bradykinin, a metabolite of the kallikrein-kinin system, has multiple actions in urinary bladders, including the ability to contract the detrusor smooth muscle, 6) stimulate sensory nerves 6,7) and evoke the release of cyclooxygenase (COX) products.8) Also, bradykinin might play a key role in the pathogenesis of experimental cystitis 9) and activation of the kallikrein-kinin system in urinary bladders of patients with interstitial cystitis has been reported. 10,11) Thus, the actions of bradykinin in urinary bladders resemble those of PAR-2 agonists.In the present study, we examined the role of bradykinin in contractions induced by trypsin and the PAR-2 agonist 2-furoyl-LIGRL-NH 2 12) in the urinary bladders from normal and CYP-induced cystitis rats. MATERIALS AND METHODS AnimalsThe protocol for the use of animals was approved by the Committee on the Care and Use of Laboratory Animals of Kitasato University.Male Wistar rats weighing 250-280 g were maintained on standard rat chow and tap water ad libitum with a 12 h light/ dark cycle in a quiet environment. Rats were treated with vehicle (saline) or CYP (150 mg/kg, intraperitoneally (i.p.)). Experiments were performed 48 h after the treatment. Preparation of Rat Urinary Bladder StripsThe rats were anesthetized with pentobarbital sodium (50 mg/kg, i.p.) and sacrificed. The urinary bladder was removed and placed in ice-cold Krebs-Ringer bicarbonate buffer (KRB, composition in mmol/l: NaCl, 119; KCl, 4.8; MgSO 4 , 1.2; KH 2 PO 4 , 1.2; CaCl 2 , 2.5; NaHCO 3 , 25 and glucose, 10.0) (pHϭ7.4). Four longitudinal strips (approximately 1 mmϫ2 mmϫ10 mm) were isolated from the bladder body.Measurement of Mechanical Activity One end of each strip was attached to an isometric force displacement transducer (model TB-611T, Nihon Kohden, Tokyo) by a cotton thread, and the other end was tied to a stainless-steel holder. Tension was digitized at a sampling rate of 2 Hz (model 15BXW-H4, Dacs Giken, Okayama) and stored on the hard disk of a personal computer. Strips were mounted in 10-ml jacketed organ baths filled with KRB gassed with 95% O 2 -5% CO 2 at 37°C. The preparations were placed under initial load (9.8 mN) and the resting tension was adjusted every 15 min. The tissues were allowed to equilibrate for 60 min and the bath fluid was changed every 15 min with fresh KRB. After the equilibration period, all preparations were contracted with acetylcholine (ACh) (100 mmol/l) to c...

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Pharmacological analysis of the local and reflex responses to bradykinin on rat urinary bladder motility in vivo

Cited by 28 publications

References 42 publications

The Use of the Isolated Mouse Whole Bladder for Investigating Bladder Overactivity

The Use of the Isolated Mouse Whole Bladder for Investigating Bladder Overactivity

Characterization of kinin receptors in human cultured detrusor smooth muscle cells

Involvement of Bradykinin in Trypsin-Induced Urinary Bladder Contraction in Cyclophosphamide-Treated Rats

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