Effects of secretagogues on ATP levels and protein carboxyl methylation in rat brain synaptosomes

Journal Article · Thu May 01 04:00:00 EDT 1986 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:5429899

Bjorndahl, J M; Rutledge, C O

The influence of various substances which are known to alter free intracellular calcium concentrations on protein carboxyl methyltransferase (PCM) activity was investigated in rat brain synaptosomes. The synaptosomes were labeled with L-(/sup 3/H)methionine and the /sup 3/H-methyl esters of proteins were formed from the methyl donor S-(/sup 3/H)adenosyl-L-methionine ((/sup 3/H)AdoMet). The calcium ionophore A23187 and ouabain decreased PCM activity and the decrease produced by A23187 was antagonized by ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid and MnCl/sub 2/. On the other hand, ruthenium red, an inhibitor of calcium uptake, stimulated PCM activity. These data suggest that PCM activity is inversely related to the free cytoplasmic calcium concentration. Veratridine, A23187 and elevated potassium ions decreased the levels of ATP and (/sup 3/H)AdoMet. The A23187-mediated decrease in ATP levels and the reduced (/sup 3/H)AdoMet formation was antagonized by ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid and MnCl/sub 2/. Inhibition of metabolic activity of the synaptosomes by NaCN led to: decreased ATP levels; inhibition of (3H)AdoMet formation; and inhibition of PCM activity. These data suggest that the decrease in protein methylation produced by secretagogues is associated with an increase in the concentration of free intracellular calcium which results in a decrease in the metabolically active pool of ATP. This leads to a decreased rate of AdoMet formation, a cosubstrate for PCM and a resultant decrease in PCM activity.

• Research Organization: Univ. of Kansas, Lawrence
• OSTI ID: 5429899
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 2; ISSN JPETA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALCOHOLS
ALKALI METAL COMPOUNDS
ALKALI METALS
ALKALINE EARTH METALS
AMINO ACIDS
ANIMALS
ATP
BIOCHEMISTRY
BODY
BRAIN
CALCIUM
CARBOHYDRATES
CARBOXYLIC ACIDS
CARDIAC GLYCOSIDES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CHELATING AGENTS
CHEMICAL REACTIONS
CHEMISTRY
CYANIDES
DRUGS
EGTA
ELEMENTS
ENZYME ACTIVITY
ENZYMES
GLYCOLS
GLYCOSIDES
HYDROXY COMPOUNDS
IN VITRO
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPOTROPIC FACTORS
MAMMALS
MANGANESE
METALS
METHIONINE
METHYLATION
NERVES
NERVOUS SYSTEM
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OUABAIN
POTASSIUM
PROTEINS
RATS
RODENTS
SODIUM COMPOUNDS
STROPHANTHINS
TRACER TECHNIQUES
TRANSFERASES
TRANSITION ELEMENTS
TRITIUM COMPOUNDS
VERTEBRATES