AMITRIPTYLINE INHIBITS THE G-PROTEIN AND K-CELL LINE( CHANNEL IN THE CLONED THYROID)

We have reported that thyroid K+ channel is activated by extracellular application of the thyroid-stimulating hormone (TSH) using single cha nnel recording method performed on cloned normal rat thyroid cell (FRT L-5) membrane. Treatment of dibutyryladenosine cyclic monophosphate (B t(2) cAMP) also activated the TSH-dependent K+ channel. These findings indicate that the thyroid K+ channel is activated through the TSH-ade nosine cyclic monophosphate (cAMP)-protein kinase A system. We examine d the effects of amitriptyline on TSH-guanosine triphosphate binding p rotein (G protein)-adenylate cyclase-cAMP-K+ channel system in the clo ned normal rat thyroid cell line FRTL-5. Amitriptyline inhibited the c AMP production induced by TSH. Amitriptyline also inhibited the cAMP p roduction induced by cholera toxin, indicating that amitriptyline inhi bited the thyroid Ci protein. Amitriptyline had no effect on TSH-recep tor binding and cAMP production by forskolin (adenylate cyclase stimul ator). Amitriptyline inhibited the K+ channel activation by cAMP, indi cating that the suppressing mechanism is not the inhibition of TSH rec eptor or G protein but the direct suppression of K+ channel. It was co ncluded that amitriptyline inhibited the thyroid G protein and K+ chan nel.