title: Beta-adrenergic potentiation of the increased in vitro accumulation of cycloleucine by rat thymocytes induced by triiodothyronine.
abstract: We have previously demonstrated that 3,5,3'-triiodothyronine (T(3)), whether administered in vivo or added to suspending media in vitro, promptly stimulates the in vitro accumulation of the nonmetabolized amino acids, alpha-aminoisobutyric acid, and cycloleucine (CLE) by thymocytes isolated from weanling rats. In these studies, we have examined the in vitro interaction between catecholamines and T(3) with respect to this effect. The previously reported enhancement of CLE accumulation in thymocytes by T(3) in vitro (1 muM) was confirmed. When added alone in concentrations ranging between 10 nM and 0.1 mM, the adrenergic agonists, epinephrine and norepinephrine, had no effect on CLE accumulation. At a concentration of 1 muM, isoproterenol, terbutaline, and phenylephrine were also without effect. However, the effect of T(3) was clearly potentiated by the concomitant addition of epinephrine, norepinephrine, and possibly isoproterenol, whereas terbutaline and phenylephrine were without effect. Neither basal nor T(3)-enhanced CLE accumulation was affected by the addition alone of the adrenergic blocking agents, propranolol (0.1 mM), phentolamine (10 muM), or practolol (0.1 mM). Nevertheless, the beta(1)- and beta(2)-antagonist, propranol, and the beta(1)-antagonist, practolol, blocked the increment in CLE accumulation produced by epinephrine; the alpha-antagonist, phentolamine, was without effect. The enhancement of CLE accumulation that occurred in the presence of T(3), with or without epinephrine, was seen to be a result of an inhibition of CLE efflux, because T(3) alone inhibited CLE efflux, and this effect was increased when epinephrine was also present. On the other hand, neither T(3) alone nor T(3) plus epinephrine appreciably altered the rate of inward transport of CLE. As judged from studies of the ability of thymocytes to exclude trypan blue, neither T(3) alone nor T(3) plus epinephrine either enhanced or impaired viability of cells during 3-h periods of incubation. Cell water content, measured with [(3)H]urea, was unaffected by T(3), either alone or in the presence of epinephrine. In confirmation of previous results, the stimulatory effect of T(3) on CLE accumulation was unaffected by concentrations of puromycin sufficient to inhibit protein synthesis by at least 95%, and the potentiating action of epinephrine on the response to T(3) was similarly unaffected. From these findings, it is concluded that the effect of T(3) to increase CLE accumulation by thymocytes in vitro, though itself independent of adrenergic mediation, is potentiated by beta(1)-adrenergic stimulation. This interaction appears distinctly different from other thyroid hormone-catecholamine interactions, in which thyroid hormones enhance physiological responses to catecholamines. Its mechanism remains unclear, but the properties of the T(3) effect, and possibly the interaction itself, suggest that T(3) enhances CLE accumulation by an action at the level of the cell membrane.
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival; D003515:Cycloleucine / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011217:Practolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011691:Puromycin / Q000494:pharmacology; D051381:Rats; D013601:T-Lymphocytes / Q000378:metabolism*; D013726:Terbutaline / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D000318:Adrenergic beta-Agonists; D000596:Amino Acids; D014284:Triiodothyronine; D003515:Cycloleucine; D011691:Puromycin; D011433:Propranolol; D007545:Isoproterenol; D013726:Terbutaline; D011217:Practolol; D004837:Epinephrine; D010646:Phentolamine