title: Effect of amitriptyline on the messenger RNA of thyroid hormone-responsive genes in rat cerebral tissue.
abstract: To determine the molecular mechanisms of the potentiating effect of thyroid hormones (TH) on the therapeutic efficacy of tricyclic antidepressants (TCA), the expression of two known TH-responsive mRNAs was measured in control rats and rats treated with triiodothyronine (T3, 10 microg/100 g for 10 days), amitriptyline (10 mg/kg for 10 days), or combined T3 and amitriptyline. Northern blot analysis was carried out to measure the cerebral tissue content of a novel translational repressor (NAT-1) and another thyroid hormone-responsive (THR) mRNA. Rats treated with the combination of T3 and amitriptyline had significantly higher NAT-1 expression (2691.1+/-134.1 arbitrary units) than rats treated with T3 only (1688.5+/-77.8) or with amitriptyline only (1452.5+/-87.5) or the untreated control rats (731.3+/-23.0), P<0.01. Amitriptyline treatment did not alter the expression of THR mRNA or THR protein in either control or T3-treated rats. It is concluded that alterations in the expression of selective T3 responsive genes in cerebral tissue could be a mechanism of the known T3 potentiation of the therapeutic efficacy of TCA.
authors.affiliation: Department of Internal Medicine, St Louis University Medical School, MO 63104, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Mooradian
authors.forename: J P
authors.initials: JP
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001835:Body Weight; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics; D018076:DNA, Complementary; D004435:Eating; D015870:Gene Expression / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D012097:Repressor Proteins / Q000235:genetics*; D014284:Triiodothyronine / Q000235:genetics / Q000494:pharmacology*
chemical_list: C109099:Abi2 protein, rat; D048868:Adaptor Proteins, Signal Transducing; D000929:Antidepressive Agents, Tricyclic; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014284:Triiodothyronine; D000639:Amitriptyline