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Local receptors as novel regulators for peripheral clock expression.

Changhao Wu1, Guiping Sui2, Simon N Archer3

  • 1Department of Biochemistry and Physiology, University of Surrey, Surrey, UK; c.wu@surrey.ac.uk.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|August 23, 2014
PubMed
Summary

Local receptors regulate the urinary bladder

Keywords:
agingcircadianmuscarinicpurinergic

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Area of Science:

  • Chronobiology
  • Physiology
  • Molecular Biology

Background:

  • Mammalian circadian rhythms are governed by the suprachiasmatic nucleus (SCN) and peripheral clocks.
  • Emerging research indicates SCN-independent regulation of peripheral clocks.
  • The urinary bladder's clock protein PERIOD 2 (PER2) dynamics and receptor influence are not well understood.

Purpose of the Study:

  • To investigate the influence of excitatory receptor activation on PER2 circadian dynamics in the urinary bladder.
  • To explore the role of aging on bladder clock regulation and receptor responsiveness.
  • To determine if bladder smooth muscle contraction exhibits circadian rhythm and its relation to receptor activity.

Main Methods:

  • Utilized PERIOD2::LUCIFERASE-knock-in mice for real-time PER2 monitoring in bladder tissue.
  • Administered muscarinic and purinergic receptor agonists to assess PER2 rhythm shifts.
  • Examined the impact of mechanical stimulation and aging on PER2 expression and response.
  • Measured circadian rhythmicity in muscarinic agonist-induced smooth muscle contraction.

Main Results:

  • Bladder wall PER2 exhibited robust circadian rhythms with a ~24-hour cycle.
  • Muscarinic and purinergic receptor activation significantly shifted PER2 peak expression earlier.
  • PER2 expression and agonist response were diminished in aged mice.
  • Smooth muscle contraction displayed circadian rhythmicity, aligning with receptor activity.

Conclusions:

  • Identified endogenous receptors as novel regulators of local bladder clock activity, independent of central SCN control.
  • Demonstrated a reciprocal alignment between the local clock and receptor activity for regulating muscle contraction.
  • Highlighted the critical role of receptor-clock interactions in maintaining physiological function.
  • Suggests dysregulation of this interaction may contribute to age-related bladder disorders.