beta(1)- and beta(3),-adrenoceptor mediated smooth muscle relaxation in hypothyroid rat ileum

The effect of hypothyroidism on gastrointestinal beta (1) - and beta (2)-ad renoceptor function and expression was examined in rat ileal smooth muscle preparations. (-)-Isoprenaline and the selective beta (3) agonist disodium (B,R)-5-[2-[[2-3-chlorophenyl)-2-hydroxyethyl]- amino]propyl]-1,3-benzodiox ole-2,2-dicarboxylate (CL 316234) relaxed both control and hypothyroid tiss ues in a dose-dependent manner. Responses to isoprenaline were reduced in t issues from hypothyroid rats, as was the shift produced with the beta (3)-a drenoceptor antagonist, 3-(2-ethylphenoxy)- 1-[(1S)-1,2,3,4-tetrahydronapht h-1-ylamino]-(2S)-2-propanol oxalate (SR 59230A). No change was seen in res ponses to CL 316243. Experiments with a selective beta (1)-adrenoceptor ant agonist produced results suggesting that isoprenaline did not act at this r eceptor. Messenger RNA levels for both beta (1)- and beta (2)-adrenoceptors were not affected by hypothyroidism. These results show that, unlike in ad ipose tissues, ileal beta (1)- and beta (3)-adrenoceptors are not directly regulated by thyroid hormone and that beta (3)-adrenoceptor coupling to the relaxation response is reduced in a rat model of hypothyroidism. (C) 2001 Elsevier Science B.V. All rights reserved.