摘要

In this study we examined whether the levels of gene expressions of the three beta-adrenergic receptor (PAR) subtypes, beta(1), beta(2), and beta(3), contribute to age-related increase in beta AR density. Liver membranes and total RNA were prepared from young (4- to 6-month-old) and old (24-month-old) male Fischer 344 rats. beta AR density (B-max) in liver membranes was measured by a radioligand receptor binding assay using the receptor subtype nonselective beta AR antagonist I-125-pindolol as the radioligand. Steady-state levels of beta(2)AR mRNA in rat liver were measured by Northern blot analysis; because of the low abundance of beta(1)AR and beta(3)AR mRNA in rat liver, the expressions of these genes were measured by a semiquantitative RT-PCR or an RT-PCR. Scatchard analysis of saturation binding curves of the binding assay confirmed an age-related increase in B-max (young: 7.1 +/- 0.8 fmol/mg protein vs. old: 18.1 +/- 4.3 fmol/mg protein). No age-related differences were found in the levels of beta(2)AR mRNA. However, semiquantitative RT-PCR revealed an approximately twofold increase in beta(1)AR mRNA level between young and old rats (P < 0.05). beta(1)AR mRNA levels were also correlated with B-max for I-125-pindolol binding sites in individual rats (r = 0.67; P = 0.012). beta(3)AR mRNA, which was demonstrable in rat white adipose tissue by RT-PCR, was generally not detected in livers from young or old rats, with the exception of two old rats with the highest B-max. These results suggest that an age-related increase of beta(1)AR gene expression contributes to increased beta AR density and beta adrenergic responsiveness in rat liver during aging.

  • 出版日期2010-2