Effect of hypothyroidism on the cytosolic free Ca 2+ concentration in rat hepatocytes during rest and following stimulation by noradrenaline or vasopressin

Abstract

The mean resting concentration of cytosolic free Ca 2+ ([Ca 2+] i) in parenchymal liver cells, as determined with the intracellular Ca 2+ indicator quin2, was lowered by about 30% in hypothyroidism (0.17 μM vs. 0.27 μM in normal cells). The [Ca 2+] i level in hypothyroid cells at 10 s following stimulation by noradrenaline (1 μM) was about 64% lower than in normal cells (0.33 μM vs. 1.0 μM). The response to noradrenaline in hypothyroid cells was slower in onset (significant at 5 s vs. 3 s in euthyroid cells), and the maximum of the initial [Ca 2+] i increase was reached later (14 s vs. 8 s in normal cells). In hypothyroid hepatocytes the initial increase was followed by a slow but prolonged secondary increase in [Ca 2+] i. With vasopressin similar results were found. Chelation of extracellular Ca 2+ with EGTA immediately prior to stimulation had no effect on the initial [Ca 2+] i increase. Treatment with T 3 in vivo (0.5 μg/100 g body weight daily during 3 days) completely restored the basal and stimulated [Ca 2+] i in hypothyroid cells. The half-maximally effective dose of noradrenaline was the same in euthyroid and hypothyroid liver cells (1.8·10 −7 M). Hypothyroidism had no significant effect on the number of α 1-receptors determined by [ 3H]prazosin labeling in crude homogenate fractions, while the K d for [ 3H]prazosin was 21% lower than in the euthyroid group. These results show that thyroid hormone has a general stimulating effect on intracellular Ca 2+ mobilization by Ca 2+-mobilizing hormones, probably at a site distal to the binding of the agonist to its receptor. The results also support our idea that thyroid hormone may control metabolism during rest and activation, at least partially, by altering Ca 2+ homeostasis.