Involvement of calmodulin and calmodulin binding site in the TSH receptor of thyroid.
Calmodulin (CaM) antagonists, W-7 and W-5, chlorpromazine and haloperidol, especially W-7 inhibited 125I-bovine TSH binding to human and porcine thyroid receptors dose-dependently in the presence of calcium ion. This inhibitory effect of W-7 was diminished by the addition of ethylenglycol tetraacetic acid (EGTA) or ethylendiamine tetraacetic acid (EDTA). CaM also dose-dependently inhibited the binding of 125I-TSH to thyroid receptor in the presence of calcium ion. TSH binding to thyroid receptor was completely inhibited by more than 30 micrograms of CaM, and this inhibition was abolished by adding EGTA. On the other hand, the antibody to CaM inhibited partially 125I-TSH binding to its receptor. These results suggest involvement of CaM and CaM-binding sites in the TSH receptor of thyroid.
Nakajima
Y
Y
Department of Internal Medicine, Nantan General Hospital, Kyoto, Japan.
Kajita
Y
Y
Ishida
M
M
Ura
Y
Y
Ochi
Y
Y
Hachiya
T
T
Hidaka
H
H
D000818:Animals; D001665:Binding Sites; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D011989:Receptors, Thyrotropin / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*; D013552:Swine; D013961:Thyroid Gland / Q000187:drug effects*
D002147:Calmodulin; D011989:Receptors, Thyrotropin; D013449:Sulfonamides; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D006220:Haloperidol; D002746:Chlorpromazine