Polarized efflux of iodide in porcine thyrocytes occurs via a cAMP-regulated iodide channel in the apical plasma membrane.
The intracellular regulation of thyrotropin-stimulated iodide efflux was studied in polarized porcine thyrocytes grown as a continuous, tight monolayer in bicameral culture chambers. From a previous study using this system we know that thyrotropin rapidly increases iodide efflux in the apical but not basal direction of the polarized epithelium. [125I]-iodide efflux in apical direction was stimulated by thyrotropin in a concentration-dependent manner (1-10 U/l), whereas efflux in basal direction was unchanged at any thyrotropin dose. Thyrotropin-induced elevation of intracellular cAMP showed a corresponding concentration dependence. The selective stimulation of apical efflux by thyrotropin was evident also when re-uptake of iodide released in basal direction was blocked by perchlorate. The effect of thyrotropin on apical efflux was mimicked by 8-bromo-cAMP and forskolin, whereas agents known to activate the Ca2+/phosphatidylinositol cascade (epidermal growth factor) and protein kinase C (phorbol ester) or increase cytosolic [Ca2+] (A23187) were inactive. We conclude that the selective stimulation by thyrotropin of apical iodide efflux, corresponding to efflux in luminal direction in intact follicles, occurs via cAMP-regulated iodide channels present in the apical domain of the plasma membrane.
Department of Anatomy, University of Göteborg, Sweden.
M
M
Nilsson
U
U
Björkman
R
R
Ekholm
L E
LE
Ericson
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D007454:Iodides / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007473:Ion Channels / Q000378:metabolism*; D008854:Microscopy, Electron; D013552:Swine; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013972:Thyrotropin / Q000494:pharmacology
D007454:Iodides; D007457:Iodine Radioisotopes; D007473:Ion Channels; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013972:Thyrotropin; D000242:Cyclic AMP