title: Antagonism between T3 and amiodarone on the contractility and the density of beta-adrenoceptors of chicken cardiac myocytes.
abstract: 3,3',5-Triiodothyronine (T3), at 10(-8) M, potentiated by 26.4-30.9% the isoproterenol-mediated inotropic effect in chick embryo cardiac myocytes in culture. Amiodarone (10(-6) M) decreased this response by 44.6% only in cells cultured with serum, where the T3 concentration was 10(-13) M. Amiodarone inhibited the potentiating effect of T3. Amiodarone alone had no influence on the beta-adrenoceptor density in cells cultured in serum-free medium. This confirms that the effects of amiodarone on cardiac beta-adrenoceptors are T3 dependent. T3 increased the density of beta-adrenoceptors through two concentration ranges, with an initial 30% increase between 10(-14) and 10(-11) M, followed by a second increase until 10(-7) M. Amiodarone not only inhibited the first positive effect of T3 but also decreased beta-adrenoceptor density far below the control value. The second positive T3 effect was also inhibited by 50% by amiodarone. This study suggests that T3 might increase the number of cell-surface beta-adrenoceptors and modify their cellular traffic through at least two mechanisms, one assumed to be non-genomic, the other being genomic, and that amiodarone could affect the two mechanisms differently.
authors.affiliation: Département de Biophysique et Pharmacologie des Biosignaux, Faculté de Médecine, Université Paris-Nord, Bobigny, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Yin
authors.forename: R
authors.initials: R
authors.lastname: Vassy
authors.forename: P
authors.initials: P
authors.lastname: Nicolas
authors.forename: G Y
authors.initials: GY
authors.lastname: Perret
authors.forename: S
authors.initials: S
authors.lastname: Laurent
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000638:Amiodarone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002642:Chick Embryo; D006321:Heart / Q000187:drug effects; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D014284:Triiodothyronine / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; D020120:Iodocyanopindolol; D010869:Pindolol; D007545:Isoproterenol; D000638:Amiodarone; C033394:CGP 12177; D002118:Calcium