Upregulation of Airway Smooth Muscle Calcium-Sensing Receptor by Low Molecular Weight Hyaluronan.

Upregulation of Airway Smooth Muscle Calcium-Sensing Receptor by Low Molecular Weight Hyaluronan. Am J Physiol Lung Cell Mol Physiol. 2020 Jan 08;: Authors: Lazrak A, Yu Z, Doran S, Jian M, Creighton J, Laube M, Garantziotis S, Prakash YS, Matalon S Abstract We investigated the mechanisms involved in the development of airway hyperresponsiveness (AHR) in mice following exposure to halogens. Male mice (C57BL/6; 20-25 g) exposed to either bromine (Br2) or Cl2 (600 or 400 ppm, respectively, for 30 min) developed AHR 24 hours post exposure. Nifedipine (an L-type calcium channel blocker) administered subcutaneously post Br2 or Cl2 exposure (5 mg/kg BW), resulted in higher AHR compared to Br2 or Cl2 alone. In contrast, diltiazem (a non-dihydropyridine L-type calcium channel blocker) decreased AHR to control (air) values. Exposure of immortalized human airway smooth muscle cells (hASMCs) to Br2 resulted in membrane potential depolarization (Vm Air: 62±3 mV; 3 h post Br2 -45±5 mV; mean±1 SEM; p<0.001), increased intracellular [Ca2+]i and increased expression of the Calcium-Sensing Receptor (Ca-SR) protein. Treatment of hASMCs with a Ca-SR siRNA significantly inhibited nifedipine induced Vm depolarization and [Ca2+]i increase in these cells; intranasal administration of an antagonist to Ca-SR in mice post Br2 exposure, reversed the effects of Br2 and nifedipine on AHR. Incubation of hASMCs with Low Molecular Weight Hyaluronan (LMW-HA), ...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research