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Cholinergic antagonists—such as antimuscarinics—are available in oral, topical, ocular, parenteral, and inhalational formulations. Most antimuscarinics are oral formulations,  while scopolamine is available as a topical patch, and ipratropium and tiotropium are available as inhalation aerosols or powders. Atropine, tropicamide, and cyclopentolate are topically instilled in the eye. Most antimuscarinics are lipid-soluble and readily absorbed from the gastrointestinal tract and...
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ENaC in Cholinergic Brush Cells.

Chrissy Kandel1, Patricia Schmidt1, Alexander Perniss1

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Summary

Mammalian urethral brush cells (UBC) can sense salt via the epithelial sodium channel (ENaC). These cholinergic cells also respond to bitter and umami stimuli, highlighting their polymodal sensory role.

Keywords:
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Area of Science:

  • Urology
  • Sensory Biology
  • Cell Physiology

Background:

  • Cholinergic urethral brush cells (UBC) are known to express bitter and umami taste signaling pathways.
  • The sensory capabilities of UBC regarding salt perception have not been fully elucidated.

Purpose of the Study:

  • To investigate the functional expression of the epithelial sodium channel (ENaC) in cholinergic UBC.
  • To determine if UBC are equipped for salt perception through ENaC.

Main Methods:

  • Isolation of cholinergic UBC from ChAT-eGFP reporter mice.
  • RT-PCR and next-generation sequencing to detect ENaC subunit mRNA expression.
  • Intracellular calcium ([Ca2+]) imaging in isolated UBC stimulated with NaCl, denatonium benzoate, and ATP.
  • Pharmacological inhibition of ENaC using amiloride.

Main Results:

  • mRNA expression of ENaC subunits (Scnn1a, Scnn1b, Scnn1g) was detected in urethral epithelium and isolated UBC.
  • Scnn1a was found in 65% of UBC and some urothelial umbrella cells.
  • Stimulation with NaCl evoked intracellular [Ca2+] increases in 70% of UBC, which were blocked by amiloride, indicating ENaC involvement.
  • UBC demonstrated polymodal responses, reacting to NaCl, bitter (denatonium), and/or umami (ATP) stimuli.

Conclusions:

  • Cholinergic UBC are functionally equipped for salt perception via amiloride-sensitive ENaC channels, specifically involving the α-ENaC subunit.
  • These findings emphasize the polymodal sensory nature of UBC, responding to diverse chemical stimuli.
  • The precise physiological role of ENaC in UBC salt perception and ion transport requires further investigation.