Inhibition of cyclic AMP formation by iodide in suspension cultures of porcine thyroid follicle cells.
In the present study porcine thyroid cells in suspension cultures were employed to investigate the suppressive effect of iodide on adenylate cyclase under basal conditions and following incubation with TSH, PGE1, cholera toxin and forskolin. Within 30 min of incubation with iodide (half-maximal effect 10(-5) M), inhibition was established and remained unchanged up to 40 h of culture. The inhibitory action was abolished by methimazole. TSH, PGE1, cholera toxin and forskolin stimulated cAMP accumulation 10-, 3-, 24- and 22-fold, respectively. Iodide pretreatment reduced basal cAMP levels and also made the cells less sensitive to stimulation by the various agents. High concentrations of TSH or PGE1 could not overcome the suppressive influence of iodide, whereas with high concentrations of cholera toxin and forskolin the reduction in cAMP levels in iodide-treated cultures was less pronounced. Membranes isolated from iodide-treated cultures produced significantly lower amounts of cAMP compared to control membranes. Furthermore, iodide did not inhibit basal or forskolin-stimulated cAMP production in human fibroblasts. The results demonstrate that iodide via an iodination-dependent mechanism influences cAMP generation in thyroid cells. It is suggested that the inhibitory activity, which has a long half-life, involves stable modification of the membrane-localized catalytic unit of adenylate cyclase such that its activation by the regulatory unit is rendered less efficient.
Heldin
N E
NE
Karlsson
F A
FA
Westermark
B
B
D000067956:Adenylyl Cyclase Inhibitors; D000527:Alprostadil; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin; D000242:Cyclic AMP / Q000096:biosynthesis*; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007454:Iodides / Q000494:pharmacology*; D008713:Methimazole / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D013552:Swine; D013961:Thyroid Gland / Q000201:enzymology*; D013972:Thyrotropin / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D004224:Diterpenes; D007454:Iodides; D011458:Prostaglandins E; D005576:Colforsin; D008713:Methimazole; D013972:Thyrotropin; D002772:Cholera Toxin; D000242:Cyclic AMP; D000527:Alprostadil