Inhibition of the Na+/I- symporter by harmaline and 3-amino-1-methyl-5H-pyrido(4,3-b)indole acetate in thyroid cells and membrane vesicles. Academic Article uri icon

Overview

MeSH

  • Animals
  • Biological Transport, Active
  • Cattle
  • Cell Line
  • Cell Membrane
  • Kinetics
  • Thyroid Gland

MeSH Major

  • Carbolines
  • Carcinogens
  • Carrier Proteins
  • Harmaline
  • Membrane Proteins
  • Symporters

abstract

  • Novel inhibitors of the Na+/I- symporter were identified using rat-thyroid-derived FRTL-5 cells and sealed vesicles from calf thyroid as model systems. Na(+)-dependent 125I- uptake was inhibited by the hallucinogenic drug harmaline and by a chemically related convulsive agent, 3-amino-1-methyl- 5H-pyrido(4,3-b)indole acetate (TRP-P-2). TRP-P-2 (Ki = 0.25 mM) was tenfold more effective as an inhibitor than harmaline (Ki = 4.0 mM). Inhibition by TRP-P-2 was competitive with respect to Na+ and was fully reversible. Although TRP-P-2 is a relatively low-affinity inhibitor, its affinity for the Na+ site of the Na+/I- symporter is over 100 times higher than that of Na+ (Km = 50 mM). 45Ca(2+)-efflux rates in calf thyroid membrane vesicles were not affected by TRP-P-2, indicating that membrane integrity is not disrupted by the drug. These findings show that TRP-P-2 may be a potentially useful tool for the identification and characterization of the Na+/I- symporter.

publication date

  • August 15, 1991

has subject area

  • Animals
  • Biological Transport, Active
  • Carbolines
  • Carcinogens
  • Carrier Proteins
  • Cattle
  • Cell Line
  • Cell Membrane
  • Harmaline
  • Kinetics
  • Membrane Proteins
  • Symporters
  • Thyroid Gland

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 1879425

Additional Document Info

start page

  • 203

end page

  • 207

volume

  • 200

number

  • 1