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. 2022 Oct;474(10):1077-1090.
doi: 10.1007/s00424-022-02736-1. Epub 2022 Jul 30.

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

Ayu Sugiura  1 , Retsu Mitsui  1 , Hikaru Hashitani  2
Affiliations

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

Ayu Sugiura et al. Pflugers Arch. 2022 Oct.

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.

Keywords: Afferent nerves; Parathyroid hormone-related protein; Transient pressure rise; Urinary bladder.

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References

    1. Moseley JM, Gillespie MT (1995) Parathyroid hormone-related protein. Crit Rev Clin Lab Sci 32:299–343. https://doi.org/10.3109/10408369509084687 - DOI - PubMed
    1. Clemens TL, Cormier S, Eichinger A, Endlich K, Fiaschi-Taesch N, Fischer E, Friedman PA, Karaplis AC, Massfelder T, Rossert J, Schlüter KD, Silve C, Stewart AF, Takane K, Helwig JJ (2001) Parathyroid hormone-related protein and its receptors: nuclear functions and roles in the renal and cardiovascular systems, the placental trophoblasts and the pancreatic islets. Br J Pharmacol 134:1113–1136. https://doi.org/10.1038/sj.bjp.0704378 - DOI - PubMed - PMC
    1. Jans DA, Thomas RJ, Gillespie MT (2003) Parathyroid hormone-related protein (PTHrP): a nucleocytoplasmic shuttling protein with distinct paracrine and intracrine roles. Vitam Horm 66:345–384. https://doi.org/10.1016/S0083-6729(03)01010-0 - DOI - PubMed
    1. Philbrick WM, Wysolmerski JJ, Galbraith S, Holt E, Orloff JJ, Yang KH, Vasavada RC, Weir EC, Broadus AE, Stewart AF (1996) Defining the roles of parathyroid hormone-related protein in normal physiology. Physiol Rev 76:127–173. https://doi.org/10.1152/physrev.1996.76.1.127 - DOI - PubMed
    1. Nishikawa N, Kanematsu A, Negoro H, Imamura M, Sugino Y, Okinami T, Yoshimura K, Hashitani H, Ogawa O (2013) PTHrP is endogenous relaxant for spontaneous smooth muscle contraction in urinary bladder of female rat. Endocrinology 154:2058. https://doi.org/10.1210/en.2012-2142 - DOI - PubMed

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