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

Abstract

Abstract

We studied the time course of cell surface β-adrenoceptors (BAR) in cardio-myocytes 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 colchichine (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.