Vasopressin inhibits type-I collagen and albumin gene expression in primary cultures of adult rat hepatocytes
The mechanisms that regulate collagen gene expression in hepatic cells are poorly understood. Accelerated Ca2+ fluxes are associated with inhibiting collagen synthesis selectively in human fibroblasts. In suspension cultures of isolated hepatocytes, the Ca2+ agonist vasopressin increases cytosolic levels of free Ca2+. However, whether vasopressin's interactions with plasma membrane V1 receptors attenuate hepatic collagen production is unknown. We investigated this problem by studying vasopressin's effects on collagen synthesis and Ca2+ efflux in long-term primary cultures of differentiated and proliferation-competent adult rat hepatocytes. Twelve-day-old quiescent cultures were exposed to test substances and labeled with (5-3H)proline. Determinations of radioactivity in collagenase-sensitive and collagenase-resistant proteins were used to calculate the relative levels of collagen production. Synthetic (8-arg)vasopressin stimulated 45Ca2+ efflux within 1 min and inhibited hepatocyte collagen production within 3 h by 50%; overall rates of protein synthesis were not affected significantly. In cultures labeled with (35S)methionine, vasopressin also decreased the levels of newly synthesized and secreted albumin, but not fibrinogen, detected in specific immunoprecipitates analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Northern blot analyses using specific (32P)cDNA probes revealed 70% decreases in hybridizable levels of collagen alpha 1(I) mRNA in hepatocyte cultures treated with either vasopressin or Ca2+ ionophore A23187; hybridizable levels of albumin mRNA also fell approximately 50% following vasopressin treatment.
- Research Organization:
- Veterans Administration Medical Center, San Diego, CA (USA)
- OSTI ID:
- 5768882
- Journal Information:
- J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 264:16; ISSN JBCHA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ALBUMINS
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
AMINES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
AUTORADIOGRAPHY
AZOLES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOASSAY
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
CALCIUM 45
CALCIUM COMPOUNDS
CALCIUM ISOTOPES
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL CULTURES
CELL MEMBRANES
COLLAGEN
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTROPHORESIS
EVEN-ODD NUCLEI
GENE REGULATION
GLUCAGON
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HORMONES
IMMUNOASSAY
INTERMEDIATE MASS NUCLEI
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LIGHT NUCLEI
LIPOTROPIC FACTORS
LIVER CELLS
MAMMALS
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
MEMBRANES
METHIONINE
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDE HORMONES
PEPTIDES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PITUITARY HORMONES
POLYPEPTIDES
PROLINE
PROTEINS
PYRROLES
PYRROLIDINES
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SCLEROPROTEINS
SOMATIC CELLS
SULFUR 35
SULFUR ISOTOPES
SYNTHESIS
TRITIUM COMPOUNDS
VASOPRESSIN
VERTEBRATES