Amitriptyline inhibits the G protein and K+ channel in the cloned thyroid cell line.
We have reported that thyroid K+ channel is activated by extracellular application of the thyroid-stimulating hormone (TSH) using single channel recording method performed on cloned normal rat thyroid cell (FRTL-5) membrane. Treatment of dibutyryladenosine cyclic monophosphate (Bt2 cAMP) also activated the TSH-dependent K+ channel. These findings indicate that the thyroid K+ channel is activated through the TSH-adenosine cyclic monophosphate (cAMP)-protein kinase A system. We examined the effects of amitriptyline on TSH-guanosine triphosphate binding protein (G protein)-adenylate cyclase-cAMP-K+ channel system in the cloned normal rat thyroid cell line FRTL-5. Amitriptyline inhibited the cAMP production induced by TSH. Amitriptyline also inhibited the cAMP production induced by cholera toxin, indicating that amitriptyline inhibited the thyroid G protein. Amitriptyline had no effect on TSH-receptor binding and cAMP production by forskolin (adenylate cyclase stimulator). Amitriptyline inhibited the K+ channel activation by cAMP, indicating that the suppressing mechanism is not the inhibition of TSH receptor or G protein but the direct suppression of K+ channel. It was concluded that amitriptyline inhibited the thyroid G protein and K+ channel.
Yoshida
A
A
First Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
Hisatome
I
I
Nawada
T
T
Sasaki
N
N
Taniguchi
S
S
Tanaka
Y
Y
Manabe
I
I
Ahmmed
G U
GU
Sato
R
R
Mori
A
A
Hattori
K
K
Ueta
Y
Y
Mitani
Y
Y
Watanabe
M
M
Igawa
O
O
Fujimoto
Y
Y
Shigemasa
C
C
D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors*; D026902:Potassium Channel Blockers; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects*; D013972:Thyrotropin / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D026902:Potassium Channel Blockers; D000639:Amitriptyline; D005576:Colforsin; D013972:Thyrotropin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins