The role of ether-a-go-go-related gene K(+) channels in glucocorticoid inhibition of adrenocorticotropin release by rat pituitary cells.
The present study investigated the role of K(+) channels in the inhibitory effect of glucocorticoid on adrenocorticotropin (ACTH) release induced by corticotropin-releasing hormone (CRH) using cultured rat anterior pituitary cells. Apamin and charybdotoxin (CTX) did not have a significant effect on ACTH release induced by CRH (1 nM). Tetraethylammonium (TEA), a broad spectrum K(+) channel blocker, increased the ACTH response to CRH only at the highest concentration (10 mM). The exposure to 100 nM corticosterone for 60 min inhibited the CRH-induced ACTH release. Neither TEA, apamin, nor CTX affected the inhibitory effect of corticosterone. In contrast, astemizole (Ast) and E-4031, ether-a-go-go-related gene (erg) K(+) channel blockers, abolished the inhibitory effect of corticosterone on CRH-induced ACTH release (1.25+/-0.10 vs. 1.45+/-0.11 ng/well at 10 microM Ast, p>0.05, 1.71+/-0.16 vs. 1.91+/-0.32 ng/well at 10 microM E-4031, p>0.05, vehicle vs. corticosterone). RT-PCR demonstrated all three subtypes of rat-erg mRNAs in the pituitary and corticosterone increased only erg1 mRNA up to 2.47+/-0.54 fold. In conclusion, erg K(+) channels were up-regulated by glucocorticoid, and have indispensable roles in delayed glucocorticoid inhibition of CRH-induced ACTH release by rat pituitary cells.
Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan.
Miho
M
Yamashita
Yutaka
Y
Oki
Kazumi
K
Iino
Chiga
C
Hayashi
Fumie
F
Matsushita
Alexander
A
Faje
Hirotoshi
H
Nakamura
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism; D052680:Corticotrophs / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D051638:Ether-A-Go-Go Potassium Channels; D005938:Glucocorticoids; D010880:Piperidines; D011725:Pyridines; D012333:RNA, Messenger; C063968:E 4031; D001030:Apamin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone