A possible role for calmodulin in human thyroid cell metabolism.
A protein which shared several characteristics with authentic calmodulin was extracted from human thyroid homogenates. The protein bound to fluphenazine--Sepharose and could be specifically eluted using EGTA. The eluted protein had a u.v. spectrum characteristic of calmodulin and migrated like authentic calmodulin with a calcium-dependent shift on sodium dodecyl sulphate polyacrylamide-gel electrophoresis. Calmodulin in thyroid cell extracts was shown to be biologically active, measured by its ability to activate a calmodulin-deficient cyclic GMP phosphodiesterase; this activation could be inhibited by trifluoperazine. A possible role for calmodulin in the action of TSH on the thyroid was demonstrated by studying the effects of phenothiazines and the naphthalene sulphonamide, W7, a more specific calmodulin inhibitor, on TSH-stimulated cyclic AMP levels in cultured thyroid cells. The phenothiazines and W7 were found to inhibit the accumulation of cyclic AMP in response to TSH in a concentration-dependent manner although low concentrations of W7 enhanced TSH-stimulated cyclic AMP accumulation.
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D002147:Calmodulin / Q000302:isolation & purification / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D011346:Prochlorperazine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D013449:Sulfonamides; D014268:Trifluoperazine; C017967:W 7; D013972:Thyrotropin; D000242:Cyclic AMP; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D011346:Prochlorperazine