Transcriptional regulation of alpha(1)-adrenoceptor gene in the rat liver during different phases of sepsis

Changes in alpha(1)-adrenoceptor (alpha(1)AR) gene expression in the rat li ver during different phases of sepsis were studied. Sepsis was induced by c ecal ligation and puncture (CLP). Septic rats exhibit two metabolically dis tinct phases: an initial hyperglycemic phase (9 h after CLP, early sepsis) followed by a hypoglycemic phase (18 h after CLP; late sepsis). The [H-3]pr azosin binding studies show that the density of alpha(1)AR was increased by 30% during the early phase while it was decreased by 24% during the late p hase of sepsis. Western blot analyses reveal that alpha(1)AR protein level was elevated by 48% during early sepsis but was decreased by 55% during lat e sepsis. Northern blot analyses depict that the steady-state level of alph a(1b)AR mRNA was enhanced by 21% during the early phase but was declined by 29% during the late phase of sepsis. Nuclear run-off assays show that the transcription rate of alpha(1b)AR gene transcript was increased by 76% duri ng early sepsis while it was decreased by 29% during late sepsis. The actin omycin D pulse-chase studies indicate that the half-life of alpha(1b)AR mRN A remained unaffected during the early and the late phases of sepsis. These findings demonstrate that during the early phase of sepsis, the increase i n the rate of transcription of alpha(1b)AR gene paralleled with the elevati ons in the alpha(1b)AR mRNA abundance and alpha(1)AR protein level, while d uring the late phase of sepsis, the decrease in the rate of transcription o f alpha(1b)AR gene coincided with the declines in the alpha(1b)AR mRNA abun dance and the alpha(1)AR protein level in the rat liver. These observations indicate that the altered expression of alpha(1)AR genes in the rat liver during the progression of sepsis was regulated transcriptionally. (C) 1999 Elsevier Science B.V. All rights reserved.