Okadaic acid inhibits the release of TSH in response to TRH and K+ from rat anterior pituitaries.
The effects of okadaic acid, a non-phorbol-12-tetradecanoate-13-acetate (non-TPA)-type tumor promoter and a potent inhibitor of protein phosphatases, on thyroid-stimulating hormone (TSH) secretion from the rat anterior pituitary were examined. Preincubation of anterior pituitaries with okadaic acid caused a time- and concentration-related decrease in a subsequent thyrotropin-releasing hormone (TRH)-stimulated TSH secretion, whereas it did not cause any changes in basal secretion of TSH. In addition, okadaic acid inhibited a subsequent high K(+)-induced TSH secretion. In contrast, ionomycin-induced TSH secretion was not inhibited by pretreatment with okadaic acid. The present results suggest that okadaic acid may block the release of TSH by inhibition of Ca2+ influx through voltage-sensitive and/or receptor-operated Ca2+ channels.
Michimata
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First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Iriuchijima
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Mori
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D000818:Animals; D004988:Ethers, Cyclic / Q000494:pharmacology*; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D004988:Ethers, Cyclic; D019319:Okadaic Acid; D015759:Ionomycin; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D010749:Phosphoprotein Phosphatases; D011188:Potassium