Abstract

Thyroid hormone status influences calcium metabolism. To elucidate the mechanism of action of thyroid hormones on transcellular transport of calcium in rat intestine, Ca2+ influx and efflux studies were carried out in brush border membrane vesicles (BBMV) and across the basolateral membrane (BLM) of enterocytes, respectively. Steady-state uptake of Ca2+ into BBMV as well as Ca2+ efflux from the BLM enterocytes was significantly increased in hyperthyroid (Hyper-T) rats and decreased in hypothyroid (Hypo-T) rats as compared to euthyroid (Eu-T) rats. Kinetic studies revealed that increase in steady state Ca2+ uptake into BBMV from hyper-T rats was fraternized with decrease in Michaelis Menten Constant (Km), indicating a conformational change in Ca2+ transporter. Further, this finding was supported by significant changes in transition temperature and membrane fluidity. Increased Ca2+ efflux across enterocytes was attributed to sodium-dependent Ca2+ exchange activity which was significantly higher in Hyper-T rats and lower in Hypo-T rats as compared to Eu-T rats. However, there was no change in Ca2+-ATPase activity of BLMs of all groups. Kinetic studies of Na+/Ca2+ exchanger revealed that alteration in Na+-dependent Ca2+ efflux was directly associated with maximal velocity (Vmax) of exchanger among all the groups. cAMP, a potent activator of Na+/Ca2+ exchanger, was found to be significantly higher in intestinal mucosa of Hyper-T rats as compared to Eu-T rats. Therefore, the results of this study suggest that Ca2+ influx across BBM is possibly modulated by thyroid hormones by mediating changes in membrane fluidity. Thyroid hormones activated the Na+/Ca2+ exchange in enterocytes possibly via cAMP-mediated pathway.

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