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Nongenomic regulation by thyroid hormone of plasma membrane ion and small molecule pumps.
- Source :
-
Discovery medicine [Discov Med] 2012 Sep; Vol. 14 (76), pp. 199-206. - Publication Year :
- 2012
-
Abstract
- The sodium/proton (Na/H) exchanger, Na,K-ATPase, and Ca2+-ATPase are membrane ion pumps whose basal activities may be regulated by local nongenomic actions of thyroid hormone and hormone analogues via a hormone receptor on plasma membrane integrin αvβ3. System A amino acid transport and the activity of P-glycoprotein (P-gp; ABCB1), a multidrug efflux pump, are also modulated by thyroid hormone and αvβ3. Where signal transduction has been studied, the presence of the hormone at the receptor is transduced by mitogen-activated protein kinase (MAPK) isoforms (ERK1/2; p38) or phosphatidylinositol 3-kinase into local actions. The existence of the cell surface receptor offers opportunities to pharmacologically modify actions of these important transport functions with nanoparticulate formulations of T4 and T3 that do not enter the cell. Such formulations may reverse complex intracellular accumulations of H+, Na+, and Ca2+ that occur in clinical settings such as ischemia. In addition, nanoparticulate tetraiodothyroacetic acid (tetrac), a thyroid hormone analogue that inhibits binding of T4 and T3 to integrin αvβ3 as well as certain other functions of the integrin, may reverse P-gp-dependent resistance to anti-cancer drugs in tumor cells.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism
Amino Acids metabolism
Animals
Antineoplastic Agents pharmacology
Calcium-Transporting ATPases metabolism
Cell Line, Tumor
Humans
MAP Kinase Signaling System
Neoplasms drug therapy
Neoplasms metabolism
Phosphatidylinositol 3-Kinases metabolism
Rats
Signal Transduction
Sodium metabolism
Sodium-Potassium-Exchanging ATPase metabolism
Cell Membrane metabolism
Gene Expression Regulation
Ions
Receptors, Thyroid Hormone metabolism
Thyroid Hormones metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1944-7930
- Volume :
- 14
- Issue :
- 76
- Database :
- MEDLINE
- Journal :
- Discovery medicine
- Publication Type :
- Academic Journal
- Accession number :
- 23021374