The involvement of protein kinase C in the inhibitory effect of methoxamine on the thyrotropin-induced release of thyroxine in mouse thyroid

Kim, Se-gon; Kim, Jin-sang

Korean Journal of Veterinary Research 1998;38(3):508-517.

Se-gon Kim, Jin-sang Kim

College of Veterinary Medicine, Chonbuk National University

Mouse 갑상선에서 thyrotropin에 의한 thyroxine 유리에 미치는 methoxamine의 억제효과에 대한 protein kinase C의 관련

김세곤, 김진상

전북대학교 수의과대학

Abstract

There is evidence that the sympathetic nervous system exerts a control on thyroid function via an adrenergic innervation of thyroid cells. Although it is clear that the inhibitory effects of catecholamines result from an activation of ${alpha}_1$-adrenoceptors, the mechanisms involved in ${alpha}_1$-stimulation are not fully understood. The effects of methoxamine and protein kinase C (PKC) activator on the release of thyroxine ($T_4$) from mouse thyroid were studied to clarify the role of PKC in the regulation of $T_4$ release in vitro. The glands were incubated in the medium, samples of the medium were assayed for $T_4$ by EIA kits. Methoxamine inhibited the TSH-stimulated $T_4$ release. This inhibition was reversed by prazosin, an ${alpha}_1$-adrenergic antagonist. Futhermore, the inhibitory effect of methoxamine on the $T_4$ release stimulated by TSH was prevented by chloroethylclonidine, an ${alpha}_{1b}$-adrenoceptor antagonist, but not by WB4101, an ${alpha}_{1a}$-adrenoceptor antagonist. Also methoxamine inhibited the forskolin-, cAMP- or IBMX-stimulated $T_4$ release. These inhibition were reversed by PKC inhibitors, such as staurosporine and $H_7$. PMA, a PKC activator, completely inhibited the TSH-stimulated $T_4$ release, and its inhibition was reversed by staurosporine and $H_7$, but not by chelerythrine. R59022 (a diacylglycerol kinase inhibitor), like methoxamine, also inhibited the TSH-stimulated $T_4$ release, and its inhibition was also reversed by staurosporine. The present study suggests that methoxamine inhibition of $T_4$ release from mouse thyroid can be induced by activation of the ${alpha}_{1b}$-adrenoceptors and that it is mediated through the ${alpha}_1$-adrenoceptor-stimulated PKC formation.

Key Words: ${alpha}_1$-adrenoceptor, thyroxine, thyroid, protein kinase C, methoxamine