beta(1)- and beta(3)-adrenoceptor mediated smooth muscle relaxation in hypothyroid rat ileum.
The effect of hypothyroidism on gastrointestinal beta(1)- and beta(3)-adrenoceptor function and expression was examined in rat ileal smooth muscle preparations. (-)-Isoprenaline and the selective beta(3) agonist disodium (R,R)-5-[2-[[2-3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL 316234) relaxed both control and hypothyroid tissues in a dose-dependent manner. Responses to isoprenaline were reduced in tissues from hypothyroid rats, as was the shift produced with the beta(3)-adrenoceptor antagonist, 3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4-tetrahydronaphth-1-ylamino]-(2S)-2-propanol oxalate (SR 59230A). No change was seen in responses to CL 316243. Experiments with a selective beta(1)-adrenoceptor antagonist produced results suggesting that isoprenaline did not act at this receptor. Messenger RNA levels for both beta(1)- and beta(2)-adrenoceptors were not affected by hypothyroidism. These results show that, unlike in adipose 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.
Brown
K J
KJ
Department of Pharmacology, Monash University, 3800, Victoria, Australia.
Summers
R J
RJ
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004149:Dioxoles / Q000494:pharmacology; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism*; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects* / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects* / Q000378:metabolism
C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004149:Dioxoles; D007093:Imidazoles; D011412:Propanolamines; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D022702:Receptors, Adrenergic, beta-3; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C049763:CGP 20712A; D007545:Isoproterenol