skip to main content

Title: Butyrate modulates the expression of. beta. -adrenergic receptor subtype in 3T3-L1 cells

In mouse 3T3-L1 fibroblasts, the glucocorticoid dexamethasone (dex) affects a switch in ..beta..-adrenergic receptor (..beta..AR) subtype expression from ..beta../sub 1/AR to ..beta../sub 2/AR and increases total ..beta..AR number. They now demonstrate a similar effect by sodium butyrate (B) and find that the combined effect of these two gene-activating agents is greater than additive suggesting different mechanisms of action on the ..beta..AR. ..beta..AR are assayed in membranes prepared from 3T3-L1 cells using the radiolabeled ..beta..AR-specific antagonist (/sup 125/I)-cyanopindolol. ..beta..AR subtype is determined by competition binding of the ..beta../sub 2/AR-selective antagonist ICI 118.551 for the radioligand. B (2-10mM) causes a dose-dependent increase in total ..beta..AR number (up to 2-fold over control) and the proportion of ..beta../sub 2/AR. B (5mM) causes a time-dependent increase in total ..beta..AR number (2-fold) and the proportion of ..beta../sub 2/AR up to 24 hr. Dex maximally increases total ..beta..AR number (2-fold) when treated for 48 hr at concentrations greater than or equal to 100nM. B (2 or 5mM) together with dex (250nM) have a greater than additive effect on total ..beta..AR number at 24 hr (1.7-fold) and at 48 hr (1.4-2.4-fold, using 5 or 10mM B and dex greater than or equal to 10nM). The proportion of ..beta../submore » 2/AR is also greater when both compounds are added together. In comparison with proprionate and valerate, B increases total ..beta..AR number and the proportion of ..beta../sub 2/AR to a greater extent and at lower concentrations. To determine a functional correlate to these findings, cells were pre-treated for 48 hr with B and/or dex, intracellular ATP labeled with /sup 3/H-adenine, followed by treatment with forskolin (10..mu..M) and ..beta..AR agonists. B caused a dramatic increase in /sup 3/H-cAMP produced compared to control and dex treatments and a greater than additive effect was again achieved when B and dex were added together.« less
Authors:
; ; ;
Publication Date:
OSTI Identifier:
6763914
Report Number(s):
CONF-8604222-
Journal ID: CODEN: FEPRA; TRN: 87-010336
Resource Type:
Conference
Resource Relation:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States); Journal Volume: 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
Research Org:
Smith Kline and French Labs., Philadelphia, PA
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; BUTYRIC ACID; BIOCHEMICAL REACTION KINETICS; SYMPATHOMIMETICS; RECEPTORS; CELL MEMBRANES; DOSE-RESPONSE RELATIONSHIPS; FIBROBLASTS; IODINE 125; LIGANDS; MICE; TIME DEPENDENCE; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ANIMAL CELLS; ANIMALS; AUTONOMIC NERVOUS SYSTEM AGENTS; BETA DECAY RADIOISOTOPES; CARBOXYLIC ACIDS; CELL CONSTITUENTS; CONNECTIVE TISSUE CELLS; DAYS LIVING RADIOISOTOPES; DRUGS; ELECTRON CAPTURE RADIOISOTOPES; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; KINETICS; LABELLED COMPOUNDS; MAMMALS; MEMBRANE PROTEINS; MEMBRANES; MONOCARBOXYLIC ACIDS; NUCLEI; ODD-EVEN NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; PROTEINS; RADIOISOTOPES; REACTION KINETICS; RODENTS; SOMATIC CELLS; VERTEBRATES 550201* -- Biochemistry-- Tracer Techniques