Control of the dog thyrocyte plasma membrane iodide permeability by the Ca(2+)-phosphatidylinositol and adenosine 3',5'-monophosphate cascades.
Protein iodination by the dog thyrocyte (a marker of thyroid hormone synthesis) is stimulated by the Ca(2+)-phosphatidylinositol and cAMP cascades. We have shown previously that H2O2 generation, a limiting step of thyroid hormone synthesis, is modulated by these two cascades. In this work, we show that the I- release from preloaded thyrocytes is also activated by agents activating the Ca(2+)-phosphatidylinositol cascade and by Ca2+ ionophores, especially in synergy with 12-O-tetradecanoylphorbol 13-acetate, a potent activator of protein kinase-C. The effect of carbachol is reduced when the extracellular Ca2+ is depleted. Thus, both arms of the Ca(2+)-phosphatidylinositol cascade, Ca2+ and diacylglycerol, acutely and synergistically activate dog thyrocyte I- release. This I- release was also accelerated by acute and chronic exposure to TSH, forskolin, or (BU)2cAMP. The chronic stimulation of I- release by TSH exposure was diminished by chronic epidermal growth factor treatment (which dedifferentiates the thyrocytes). In addition, the chronic stimulation of I- release by forskolin was not affected by withdrawal of the agent up to 4 h before the experiment, in contrast to the acute effect of forskolin, which vanished within 16 min after forskolin withdrawal. These results suggest that the chronic stimulation of I- release by TSH or forskolin involves a stable mechanism. The I- transport system causing the release of I- from the dog thyrocyte is almost insensitive to inhibition by NaClO4 and KSCN. Hence, the iodide release cannot be due to the action of the basolateral Na+/I- cotransporter. In addition, we show that I- release was less sensitive than I- uptake to the inhibition by dysidenin, a marine toxin isolated from the sponge, Dysidea herbacea, known to inhibit I- uptake by dog thyroid slices. In summary, this work suggests that in a well defined model of the thyroid, the dog thyrocyte in primary culture, an I- transport system distinct from the basolateral Na+/I- cotransporter, is responsible for the observed I- release. The complex modulation of this transport system, involving at least the Ca(2+)-phosphatidylinositol and cAMP cascades, parallels the regulation of protein iodination, which itself reflects thyroid hormone synthesis.
Raspé
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Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucléaire, Free University of Brussels School of Medicine (U.L.B.), Belgium.
Dumont
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JE
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004285:Dogs; D066298:In Vitro Techniques; D007454:Iodides / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D008387:Marine Toxins / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D027981:Symporters; D013844:Thiazoles / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000099209:Sodium-Iodide Symporters
D002118:Calcium; D002352:Carrier Proteins; D000242:Cyclic AMP; D007454:Iodides; D008387:Marine Toxins; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D027981:Symporters; D013844:Thiazoles; D000099209:Sodium-Iodide Symporters; C063771:dysidenin