Defense Date

2017

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology and Biophysics

First Advisor

Vijay Lyall

Abstract

The amiloride-sensitive epithelial Na+ channel, ENaC, is the Na+-specific salt taste receptor in rodents. Compared to rodents, human salt taste perception is amiloride-insensitive. In rodents the ENaC is composed of aβg-subunits. Whereas humans express an additional subunit, the d-ENaC subunit. ENaC in human taste cells is composed of aβg-subunits or dβg-subunits, with the latter being amiloride-insensitive. Currently, it is not known if dβg-ENaC expression and trafficking is regulated by hormones and their downstream intracellular signaling effectors. The aim of this study is to investigate if arginine vasopressin (AVP), aldosterone, and cAMP regulate d-ENaC expression and trafficking in cultured fungiform human taste cells (HBO cells). Secondly, we want to demonstrate the expression of downstream signaling effectors involved in the trafficking of d-ENaC in HBO cells. Using molecular and immunocytochemical techniques, our results demonstrate that AVP, cAMP, and aldosterone increase expression of d-ENaC mRNA and protein in HBO cells. Furthermore, AVP, cAMP and aldosterone increased trafficking of the d-ENaC subunit from the cytosolic compartment to the apical pole of the HBO cells. Our results further demonstrate that HBO cells express several components of signaling cascade involved in ENaC translocation from cytosol to apical pole in HBO cells. The components of this signaling cascade include AVPR2, PKA, CREB, SGK-1, Nedd4-2, and GILZ-1. These hormones in mice and rats upregulate ENaC. Currently, we are not sure if these hormones affect ENaC this way in humans. By studying d-ENaC with these hormones, we are able to see how human ENaC is regulated in the tongue.


Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

6-27-2017

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