Functional Expression of a Ca(2+)-activated Cl(-) Channel Modulator Involved in Ion Transport and Epithelial Cell Differentiation.

Functional Expression of a Ca(2+)-activated Cl(-) Channel Modulator Involved in Ion Transport and Epithelial Cell Differentiation. Yakugaku Zasshi. 2016;136(3):485-90 Authors: Yamazaki J Abstract   Cl(-)-permeable channels and transporters expressed on the cell membranes of various mammalian cell types play pivotal roles in the transport of electrolytes and water, pH regulation, cell volume and membrane excitability, and are therefore expected to be useful molecular targets for drug discovery. Both TMEM16A (a possible candidate for Ca(2+)-regulated Cl(-) channels recently identified) and cystic fibrosis transmembrane conductance regulator (CFTR) (or cAMP-regulated Cl(-) channels) have been known to be involved in Cl(-) secretion and reabsorption in the rat salivary gland. Crosstalk between two types of regulatory pathways through these two types of channels has also been described. Previously, we demonstrated that CLCA, a Ca(2+)-activated Cl(-) channel modulator, was involved in Cl(-) absorption in rat salivary ducts. In addition to Ca(2+), basal NF-κB activity in a mouse keratinocyte line was shown to be involved in the transcriptional regulation of CLCA. Conversely, a truncated isoform of CLCA was found in undifferentiated epithelial cells present in the rat epidermal basal layers. Under regulation by Ca(2+) and PKC, the surface expression of β1-integrin and cell adhesion were decreased in the CLCA-overexpressing cells. Knockdo...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research