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Role of PTHrP in attenuating transient pressure rises and associated afferent nerve activity of the rat bladder

  • Muscle Physiology
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Abstract

Parathyroid hormone-related protein (PTHrP) released from detrusor smooth muscle (DSM) as the bladder fills acts as an endogenous DSM relaxant to facilitate bladder storage function. Here, the effects of exogenous PTHrP on transient pressure rises (TPRs) in the bladder and associated afferent nerve activity during bladder filling were investigated. In anaesthetized rats, changes in the intravesical pressure were measured while the bladder was gradually filled with saline. Afferent nerve activity was simultaneously recorded from their centrally disconnected left pelvic nerves. In DSM strips, spontaneous and nerve-evoked contractions were isometrically recorded. The distribution of PTHrP receptors (PTHrPRs) in the bladder wall was also examined by fluorescence immunostaining. The bladders in which the contralateral pelvic nerve was also centrally disconnected developed nifedipine, an L-type voltage-dependent Ca2+ channel blocker-sensitive TPRs (< 3 mmHg). Intravenous administration of PTHrP suppressed these TPRs and associated bursts of afferent nerve activity. In the bladders with centrally connected contralateral pelvic nerves, atropine, a muscarinic receptor antagonist-sensitive large TPRs (> 3 mmHg) developed in the late filling phase. PTHrP diminished the large TPRs and corresponding surges of afferent nerve activity. In DSM strips, bath-applied PTHrP (10 nM) suppressed spontaneous phasic contractions, while less affecting nerve-evoked contractions. PTHrPRs were expressed in DSM cells but not in intramural nerve fibers. Thus, PTHrP appears to suppress bladder TPRs and associated afferent nerve activity even under the influence of low degree of parasympathetic neural input during storage phases. Endogenous PTHrP may indirectly attenuate afferent nerve activity by suppressing TPRs to facilitate urinary accommodation.

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Data availability

Data is available on demand from Professor Hikaru Hashitani in whose laboratory this research was undertaken.

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Acknowledgements

The authors are grateful to Dr Naoki Aizawa (Dokkyo Medical University) for his dedicated support in afferent nerve recordings, and also thank Dr Richard Lang (Monash University) for his critically reading of the manuscript.

Funding

This research was funded by Grants-in-Aid for Scientific Research < KAKENHI > (C), Grant/Award Number (20K09564) to H.H.

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  1. Department of Cell Physiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan

    Ayu Sugiura, Retsu Mitsui & Hikaru Hashitani

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Contributions

Conceptualisation: Hikaru Hashitani; methodology: Ayu Sugiura, Retsu Mitsui, and Hikaru Hashitani; formal analysis and investigation: Ayu Sugiura, Retsu Mitsui, and Hikaru Hashitani; writing — review and editing: Ayu Sugiura, Retsu Mitsui, and Hikaru Hashitani.

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Correspondence to Hikaru Hashitani.

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Ethics approval and consent to participate

The procedures described have been approved by the animal experimentation ethics committee at the Nagoya City University Medical School. Consent to participate is “Not applicable” as human study is not included in this work.

Human and animal ethics

Experiments were carried out in accordance with the Care and Use of Animals in the Field of Physiological Sciences set out by the Physiological Society of Japan (2015). Human Ethics is “Not applicable” as human study is not included in this work.

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The authors hereby consent to publication of the Work in Pflügers Archiv European Journal of Physiology.

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The authors declare no competing interests.

Authors’ information

Hikaru Hashitani, M.D., Ph.D., Professor, Department of Cell Physiology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467–8601, Japan, Phone: + 81–52-8538131, Fax: + 81–52-8421538, Email address: hasitani@med.nagoya-cu.ac.jp.

Ayu Sugiura, M.D., Ph.D. student, Department of Cell Physiology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467–8601, Japan, Phone: + 81–52-8538131, Fax: + 81–52-8421538, Email address: o1.12rosie34.ayu@gmail.com.

Retsu Mitsui, Ph.D., lecturer, Department of Cell Physiology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467–8601, Japan, Phone: + 81–52-8538131, Fax: + 81–52-8421538, Email address: mitsui@med.nagoya-cu.ac.jp.

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424_2022_2736_MOESM1_ESM.jpg

Supplementary Fig 1. The ineffectiveness of PTHrP antagonist on TPRs or afferent firing during bladder filling In centrally-disconnected bladders (N = 3), the bolus administration of PTHrP (7-34) (500 µg/kg body weight) did not affect the amplitude (a), rate of rise (b) or frequency (c) of TPRs or afferent nerve firing during bladder filling (d). Mean ± SD. n.s., PTHrP (7-34) vs. control (JPG 220 KB)

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Sugiura, A., Mitsui, R. & Hashitani, H. Role of PTHrP in attenuating transient pressure rises and associated afferent nerve activity of the rat bladder. Pflugers Arch - Eur J Physiol 474, 1077–1090 (2022). https://doi.org/10.1007/s00424-022-02736-1

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