title: Nongenomic regulation by thyroid hormone of plasma membrane ion and small molecule pumps.
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.
authors.affiliation: Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, New York 12208, USA.
authors.forename: Hung-Yun
authors.initials: HY
authors.lastname: Lin
authors.forename: Heng Yuan
authors.initials: HY
authors.lastname: Tang
authors.forename: Faith B
authors.initials: FB
authors.lastname: Davis
authors.forename: Shaker A
authors.initials: SA
authors.lastname: Mousa
authors.forename: Sandra
authors.initials: S
authors.lastname: Incerpi
authors.forename: Mary K
authors.initials: MK
authors.lastname: Luidens
authors.forename: Ran
authors.initials: R
authors.lastname: Meng
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Davis
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007477:Ions; D020935:MAP Kinase Signaling System; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000596:Amino Acids; D000970:Antineoplastic Agents; D000252:Calcium-Transporting ATPases; D007477:Ions; D019869:Phosphatidylinositol 3-Kinases; D011988:Receptors, Thyroid Hormone; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D013963:Thyroid Hormones