Phorbol esters inhibit agonist-induced (/sup 3/H) inositol-1-phosphate accumulation in rat hippocampal slices
In rat hippocampal slices, carbachol and norepinephrine induce an accumulaton of (/sup 3/H)-inositol-1-phosphate which is markedly amplified in the presence of lithium. The tumor-promoting agents phorbol 12, dilat 13 dibutyrate (PDB) and 4..beta.. phorbol, 12..beta..-myristate, 13 ..cap alpha..-acetate (PMA) have no effect on (/sup 3/H) inositol-1-phophate accumulation alone, but when preincubated with hippocampal slices significantly inhibit the accumulation of (/sup 3/H)-inositol-1-phosphate induced by carbachol and norepinephrine. The IC/sub 50/ values of PDB and PMA are 0.2 ..mu..M and 25..mu..M respectively. In contrast, the weak tumor promoting agents 4-O-methylphorbol 12 myristate 13 acetate (MPMA) and phorbol 13,20-diacetate (P 13,20 DA) only slightly attenuate the agonist-induced response at concentrations less than or equal to100..mu..M, whereas 4..cap alpha..-phorbol (4..cap alpha..-PHR), a biologically inactive phorbol, has no effect. These data suggest that phorbol ester receptor-mediated events may be negatively coupled to agonist-induced phosphatidylinositol hydrolysis. 17 references, 3 figures.
- Research Organization:
- National Inst. of General Medical Sciences, Bethesda, MD
- OSTI ID:
- 5934857
- Journal Information:
- Biochem. Biophys. Res. Commun.; (United States), Journal Name: Biochem. Biophys. Res. Commun.; (United States) Vol. 123:2; ISSN BBRCA
- Country of Publication:
- United States
- Language:
- English
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560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADRENAL HORMONES
ALKALI METALS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL EFFECTS
BODY
BRAIN
CARBAMATES
CARBONIC ACID DERIVATIVES
CARBOXYLIC ACID SALTS
CARCINOGENS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CHEMICAL BONDS
DRUGS
ELEMENTS
ESTERS
HIPPOCAMPUS
HORMONES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LITHIUM
MAMMALS
METALS
NERVOUS SYSTEM
NEUROREGULATORS
NORADRENALINE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHORBOL ESTERS
PROMOTERS
RATS
RECEPTORS
RODENTS
STEROID HORMONES
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR PROMOTERS
VERTEBRATES