Receptor-mediated inhibition of adenylate cyclase and stimulation of arachidonic acid release in 3T3 fibroblasts. Selective susceptibility to islet-activating protein, pertussis toxin

Journal Article · Tue Jun 25 04:00:00 EDT 1985 · J. Biol. Chem.; (United States)

OSTI ID:6528979

Murayama, T; Ui, M

Thrombin exhibited diverse effects on mouse 3T3 fibroblasts. It (a) decreased cAMP in the cell suspension, (b) inhibited adenylate cyclase in the Lubrol-permeabilized cell suspension in a GTP-dependent manner, increased releases of (c) arachidonic acid and (d) inositol from the cell monolayer prelabeled with these labeled compounds, (e) increased /sup 45/Ca/sup 2 +/ uptake into the cell monolayer, and (f) increased /sup 86/Rb/sup +/ uptake into the cell monolayer in a ouabain-sensitive manner. Most of the effects were reproduced by bradykinin, platelet-activating factor, and angiotensin II. The receptors for these agonists are thus likely to be linked to three separate effector systems: the adenylate cyclase inhibition, the phosphoinositide breakdown leading to Ca/sup 2 +/ mobilization and phospholipase A2 activation, and the Na,K-ATPase activation. Among the effects of these agonists, (a), (b), (c), and (e) were abolished, but (d) and (f) were not, by prior treatment of the cells with islet-activating protein (IAP), pertussis toxin, which ADP-ribosylates the Mr = 41,000 protein, the alpha-subunit of the inhibitory guanine nucleotide regulatory protein (Ni), thereby abolishing receptor-mediated inhibition of adenylate cyclase. The effects (a), (c), (d), and (e) of thrombin, but not (b), were mimicked by A23187, a calcium ionophore. The effects of A23187, in contrast to those of receptor agonists, were not affected by the treatment of cells with IAP. Thus, the IAP substrate, the alpha-subunit of Ni, or the protein alike, may play an additional role in signal transduction arising from the Ca/sup 2 +/-mobilizing receptors, probably mediating process(es) distal to phosphoinositide breakdown and proximal to Ca/sup 2 +/ gating.

• OSTI ID: 6528979
• Journal Information: J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 12; ISSN JBCHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACID ANHYDRASES
ALKALI METAL ISOTOPES
ALKALINE EARTH ISOTOPES
ANGIOTENSIN
ANIMAL CELLS
ANIMALS
ANTIGENS
ARACHIDONIC ACID
ATP-ASE
BACTERIA
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BLOOD COAGULATION FACTORS
BRADYKININ
CALCIUM 45
CALCIUM ISOTOPES
CARBOHYDRATES
CARBOXYLIC ACIDS
CARDIOVASCULAR AGENTS
CATIONS
CELL CONSTITUENTS
CELL MEMBRANES
CHARGED PARTICLES
CHLORIDES
CHLORINE COMPOUNDS
COAGULANTS
CONNECTIVE TISSUE CELLS
CYCLASES
DAYS LIVING RADIOISOTOPES
DRUGS
ENZYME ACTIVITY
ENZYMES
EVEN-ODD NUCLEI
FIBROBLASTS
GLOBULINS
HALIDES
HALOGEN COMPOUNDS
HEMATOLOGIC AGENTS
HEMOSTATICS
HYDROGEN ISOTOPES
HYDROLASES
INOSITOL
INOSITOLS
INTERMEDIATE MASS NUCLEI
IONS
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
KININS
LIGHT NUCLEI
LYASES
MAMMALS
MATERIALS
MEMBRANES
MICE
MICROORGANISMS
MINUTES LIVING RADIOISOTOPES
MONOCARBOXYLIC ACIDS
MONOSACCHARIDES
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
PEPTIDES
PHOSPHOHYDROLASES
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RODENTS
RUBIDIUM 86
RUBIDIUM ISOTOPES
SACCHARIDES
SENSITIVITY
SERINE PROTEINASES
SOMATIC CELLS
THROMBIN
TOXIC MATERIALS
TOXINS
TRACER TECHNIQUES
TRITIUM
VASOCONSTRICTORS
VERTEBRATES
YEARS LIVING RADIOISOTOPES