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Concomitant alteration in number and affinity of P2X and muscarinic receptors are associated with bladder dysfunction in early stage of diabetic rats

  • Urology - Original Paper
  • Published:
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Abstract

Objectives

To investigate time course of bladder dysfunction and concurrent changes in number and affinity of the muscarinic and P2X receptor in the early stage of streptozotocin (STZ)-induced diabetic rats.

Materials and methods

Diabetic rats were prepared by the intraperitoneal injection of 50 mg/kg of STZ to 7-week-old female Wistar rats. We performed recording of 24-h voiding behavior and cystometry at 1, 4, 8, and 12 weeks after the induction of diabetes. A muscle strip experiments with electrical field stimulation (EFS), carbachol, and α,β-methylene adenosine 5′-triphosphate (α,β-MeATP) were also performed at the same time-points. Additionally, concurrent changes in number and affinity of bladder muscarinic and P2X receptor were measured by a radioreceptor assay using [N-methyl-3H] scopolamine methyl chloride ([3H]NMS) and α,β-methylene-ATP (2,8-3H) tetrasodium salt ([3H]α,β-MeATP).

Results

In STZ-induced diabetic rats, polydipsic polyuric pollakiuria were noted on recording of 24-h voiding behavior from early stage. Also, the residual urine volume markedly increased in diabetic rats on cystometry. In the muscle strip experiment, the detrusor contractions induced by EFS, carbachol, and α,β-MeATP were enhanced in STZ-induced diabetic rats. Based on the radioreceptor assay, the maximum number of sites (Bmax) for the specific binding of [3H]NMS and [3H]α,β-MeATP was concurrently increased in the bladder from diabetic rats.

Conclusion

Increased bladder contractility is found in early stage of diabetic rats. Then, bladder dysfunction is associated with increased number of muscarinic and P2X receptors in STZ-induced diabetic rats.

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Abbreviations

STZ:

Streptozotocin

EFS:

Electrical field stimulation

α,β-MeATP:

α,β-methylene adenosine 5′-triphosphate

[3H]NMS:

[N-methyl-3H] scopolamine methyl chloride

[3H]α,β-MeATP:

α,β-methylene-ATP (2,8-3H) tetrasodium salt

Kd:

Dissociation constant

Bmax:

Maximum number of sites

NANC:

Non-adrenergic non-cholinergic

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Authors and Affiliations

  1. Department of Urology, Nihon University School of Medicine, 30-1, Oyaguchikamicho, Itabashi-ku,, Tokyo, 173-8610, Japan

    Tsuyoshi Yoshizawa, Kenya Yamaguchi & Satoru Takahashi

  2. Taiho Pharmaceutical Co., Ltd., Tsukuba, Japan

    Yukio Hayashi & Shohei Yoshida

  3. Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

    Akira Yoshida, Yoshihiko Ito & Shizuo Yamada

Authors
  1. Tsuyoshi Yoshizawa
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  2. Yukio Hayashi
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  3. Akira Yoshida
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  4. Shohei Yoshida
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  5. Yoshihiko Ito
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  6. Kenya Yamaguchi
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  8. Satoru Takahashi
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Correspondence to Satoru Takahashi.

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The authors declare that they have no conflict of interest.

Ethical approval

All animal experiments were approved by the Animal Research and Care Committee at the Nihon University School of Medicine (Approved No. 080139). This article does not contain any studies with human participants performed by any of the authors.

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Yoshizawa, T., Hayashi, Y., Yoshida, A. et al. Concomitant alteration in number and affinity of P2X and muscarinic receptors are associated with bladder dysfunction in early stage of diabetic rats. Int Urol Nephrol 50, 451–458 (2018). https://doi.org/10.1007/s11255-018-1800-6

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  • DOI: https://doi.org/10.1007/s11255-018-1800-6

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