Effect of calmodulin inhibitors on thyroid hormone secretion.
The effect of calmodulin inhibitors, N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) and trifluoperazine, on TSH-induced thyroid hormone secretion from rat thyroid was examined in vivo and in vitro. The ip administration of 5 mg W-7 to the rat inhibited T4 and T3 secretion from rat thyroids at 2, 3, and 4 h after the ip injection of 2 IU TSH, and so did the ip injection of trifluoperazine at 3 and 4 h. However, the ip injection of N-(6-aminohexyl)-1-naphthalene sulfonamide as a control substance did not show any significant inhibition of T4 and T3 release. To identify the site of action of calmodulin, the effect of W-7 on (Bu)2cAMP-induced thyroid hormone secretion was tested in vitro. One hundred micromolar W-7 completely inhibited T4 release from the rat thyroid when it was enhanced by TSH or (Bu)2cAMP, suggesting that the inhibitory effect of W-7 is subsequent to cAMP formation. These results suggest that calmodulin may play a role in thyroid hormone secretion from the thyroid, acting beyond cAMP formation.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D000242:Cyclic AMP / Q000096:biosynthesis; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism; D013997:Time Factors; D014268:Trifluoperazine / Q000494:pharmacology; D014284:Triiodothyronine / Q000378:metabolism
D002147:Calmodulin; D013449:Sulfonamides; D013963:Thyroid Hormones; D014284:Triiodothyronine; D014268:Trifluoperazine; D003994:Bucladesine; C017967:W 7; D000242:Cyclic AMP; D013974:Thyroxine