Age-related increase of beta1-adrenergic receptor gene expression in rat liver: a potential mechanism contributing to increased beta-adrenergic receptor density and responsiveness during aging.
In this study we examined whether the levels of gene expressions of the three beta- adrenergic receptor (betaAR) subtypes, beta(1), beta(2), and beta(3), contribute to age-related increase in betaAR density. Liver membranes and total RNA were prepared from young (4- to 6-month-old) and old (24-month-old) male Fischer 344 rats. betaAR density (B(max)) in liver membranes was measured by a radioligand receptor binding assay using the receptor subtype nonselective betaAR antagonist (125)I-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) values for (125)I-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 betaAR density and beta adrenergic responsiveness in rat liver during aging.
Jin
Wei
W
GRECC, Audie L. Murphy Memorial Veterans Hospital, and Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. mazwang@fudan.edu.cn
D000375:Aging / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D018507:Gene Expression Regulation, Developmental; D008099:Liver / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011916:Rats, Inbred F344; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3