Cysteamine-induced decrease of somatostatin in rat brain synaptosomes in vitro

Journal Article · Thu Oct 01 04:00:00 EDT 1987 · Endocrinology; (United States)

OSTI ID:5857028

Widmann, R; Sperk, G

The mechanism of somatostatin depletion induced by cysteamine (2-mercaptoethylamine (CySH)) was studied in isolated nerve endings (synaptosomes) from rat brain in vitro. A dose-dependent reduction of somatostatin-like immunoreactivity (SLI) was observed which reached its maximal extent (41%) at a concentration of 300 microM CySH after 1-5 min. There was no release of somatostatin into the incubation medium. CySH at concentrations of up to 10 mM did not interfere in the RIA. Among a variety of compounds, structurally related to CySH 4-aminothiophenol, 2-aminothiophenol and N,N-dimethylaminothiol exhibited the highest efficacy in decreasing somatostatin. The disulfide form of CySH cystamine and dimercaprol resulted in about 15% reduction after 10-min incubation, whereas taurine, alanine, cysteine, and mercaptoethanol were inactive. A saturable, sodium-dependent uptake process was found for the disulfide form of (/sup 35/S)CySH cystamine (Michaelis-Menten constant (Km) = 18.6 microM, maximum velocity (Vmax) = 2.3 nmol/mg protein X 3 min) which was inhibited by cysteine (87% at 1 mM). (/sup 35/S)CySH, at concentrations of 20 microM or less, was not stable in buffer solution. It underwent considerable nonenzymatic conversion into its dimeric form (60% at 37 C and 3 min), however it exhibited the same kinetic data for its uptake. Size exclusion HPLC of purified hypothalamic synaptosomes revealed a major SLI peak coeluting with synthetic somatostatin-14 and two minor peaks representing somatostatin-28 and a 13,000 mol wt protein. The three molecular forms of somatostatin were reduced to varied extent by CySH. Our experiments suggest that high affinity uptake of CySH may precede its action in decreasing somatostatin levels.

• Research Organization: Univ. of Innsbruck, Austria
• OSTI ID: 5857028
• Journal Information: Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 121:4; ISSN ENDOA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL FUNCTIONS
BIOSYNTHESIS
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
CHROMATOGRAPHY
CYSTAMINE
DAYS LIVING RADIOISOTOPES
DISPERSIONS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
EVEN-ODD NUCLEI
FUNCTIONS
IN VITRO
ISOTONIC SOLUTIONS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MIXTURES
NERVE CELLS
NERVOUS SYSTEM
NUCLEI
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RATS
REDOX REACTIONS
RODENTS
SEPARATION PROCESSES
SOLUTIONS
SOMATIC CELLS
SOMATOSTATIN
SULFUR 35
SULFUR ISOTOPES
SYNTHESIS
TRACER TECHNIQUES
VERTEBRATES