Analysis of the daily changes of melatonin receptors in the rat liver

作者:Venegas Carmen; Garcia Jose A; Doerrier Carolina; Volt Huayqui; Escames Germaine; Lopez Luis C; Reiter Russel J; Acuna Castroviejo Dario*
来源:Journal of Pineal Research, 2013, 54(3): 313-321.
DOI:10.1111/jpi.12019

摘要

Melatonin membrane (MT1 and MT2) and nuclear (ROR) receptors have been identified in several mammalian tissues, including the liver. The mechanisms regulating hepatic melatonin receptors are yet unknown. This study investigated whether these receptors exhibit daily changes and the effects of melatonin on their levels. Our results show that mRNAs for MT1/MT2 receptors exhibit circadian rhythms that were followed by rhythms in their respective protein levels; the acrophases for the two rhythms were reached at 04:00 and 05:00hr, respectively. Pinealectomy blunted the rhythms in both mRNAs and protein levels. In contrast, mRNA and protein levels of nuclear receptor ROR increased significantly after pinealectomy. The cycles of the latter receptor also exhibited circadian rhythms which peaked at 03:00 and 03:45hr, respectively. Melatonin administration (10200mg/kg) increased in a dose-dependent manner the protein content of MT1/MT2 receptors, with no effects on ROR. Lunzindole treatment, however, did not affect melatonin receptor expression or content of either the membrane or nuclear receptors. Together with previously published findings which demonstrated the intracellular distribution of melatonin in rat liver, the current results support the conclusion that the circadian rhythms of MT1/MT2 and ROR receptors are under the control of the serum and intracellular melatonin levels. Moreover, the induction of MT1/MT2 receptors after the administration of high doses of melatonin further suggests that the therapeutic value of melatonin may not be restricted to only low doses of the indoleamine.

  • 出版日期2013-4