Nongenomic Effect of Triiodothyronine on Cell Surface  -Adrenoceptors in Cultured Embryonic Cardiac Myocytes

Abstract

We studied the time course of cell surface beta-adrenoceptors (BAR) in cardiomyocytes in response to a single triiodothyronine (T3) (10(-8) M) stimulation. An early first increase of BAR density was observed within 2 hr (+ 10% versus control cells, P < 0.05), and a plateau was maintained for 17-20 hr. This effect was followed by a much greater, late increase of BAR density, starting around 22 hr and lasting until 48 hr post T3 addition (+40% versus control cells; p < 0.05). Since reverse T3 studied in the same conditions had no effect in this system, we concluded that this T3 effect was specific. We hypothesized that the early response might be nongenomic because the early effect of T3 was still observed in the presence of cycloheximide (2 x 10(-5) M) whereas the late increase was totally suppressed by the drug. The early response to T3 required intact microtubules, since colchicine (2 x 10(-5) M) was able to block the increase in the cell surface BAR number, but it did not involve a change in BAR distribution between external and internal sites, as the external to total BAR ratio remained stable. The measurement of the rate of BAR disappearance from the cell surface allowed us to hypothesize that T3 induced a modification of the turnover in cell surface BAR.

Nongenomic signaling pathways triggered by thyroid hormones and their metabolite 3‐iodothyronamine on the cardiovascular system

“…However, other studies using chick embryonic ventricular myocytes showed that the b1R density was slightly enhanced only 2 h after T 3 addition, this action being blocked by colchicines, which suggests the involvement of microtubules and that T 3 is also able to enhance the myocyte sensitivity to catecholamines by nongenomic mechanisms (Vassy et al, 1997).…”

“…Most of these processes are described to be mediated by the classic genomic mechanism of steroid hormone action that takes days or months to be effective, once dependent on gene transcription. However, recent studies have shown that T 3 also acts in minutes to hours leading to changes in cardiac inotropism, chronotropism, and hypertrophy through receptors placed in the membrane and at other subcellular sites (Rudinger et al, 1984;Mylotte et al, 1985;Craelius et al, 1990;Sakaguchi et al, 1996;Vassy et al, 1997;Incerpi et al, 1999;Sun et al, 2000;Quesada et al, 2002;Schmidt et al, 2002;Wang et al, 2003;Kuzman et al, 2005;Kenessey and Ojamaa, 2006;Storey et al, 2006;Zinman et al, 2006).…”

Nongenomic Steroid Action: Controversies, Questions, and Answers

“…T 3 treatment was also found to lower the prevalence of atrial fibrillation in artery bypass graft patients, an effect that may be explained by the rapid response of some voltage-gated K ϩ channels to thyroid hormones (234,417). An early nongenomic, cycloheximide-insensitive modulation of ␤-adrenoreceptor density by T 3 has been seen in cultured embryonic cardiomyocytes (496), while the late-phase ␤-adrenoreceptor upregulation was cycloheximide sensitive. This adrenoreceptor modulation may explain the T 3 -dependent sensitization of ␤-adrenergic inotropy (507) by increasing ␤-adrenoreceptor signal transduction and cAMP production, whereas T 3 alone does not affect cAMP (508).…”

Abnormal thyroid function is common in takotsubo syndrome and depends on two distinct mechanisms: results of a multicentre observational study

“…This applies to psychosocial stressors, physical strain and autonomous production of catecholamines by pheochromocytomas and paragangliomas, as demonstrated in a recent meta-analysis [50]. Thyroid hormones are able to sensitize the heart for catecholamines by stimulating the expression of beta-adrenoceptors in cardiomyocytes, with subsequent positive inotropic and chronotropic effects [25,35,36,37]. Therefore, an excess of thyroid hormones might potentiate the effects of catecholamines in the myocardial tissue with resulting increased sensibility to stress events and heart stunning [38][39][40].…”