Nongenomic effect of triiodothyronine on cell surface beta-adrenoceptors in cultured embryonic cardiac myocytes.
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.
Vassy
R
R
Laboratory of Clinical and Experimental Pharmacology, UFR Léonard-de-Vinci, Bobigny, France.
Nicolas
P
P
Yin
Y L
YL
Perret
G Y
GY
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D003078:Colchicine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D020120:Iodocyanopindolol; D008870:Microtubules; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011433:Propranolol / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology*
D011500:Protein Synthesis Inhibitors; D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; D020120:Iodocyanopindolol; D003513:Cycloheximide; D011433:Propranolol; D010869:Pindolol; D003078:Colchicine