Stimulus-response coupling in platelets

Thesis/Dissertation · Wed Jan 01 04:00:00 EST 1986

OSTI ID:6974541

Huang, E M

To understand the mechanism of stimulus-response coupling in platelets, the potentiating effect of succinate and lithium on platelet activation was examined. The action of succinate was immediate; preincubation with succinate did not lead to desensitization. Succinate was comparable to ADP in lowering cAMP levels previously elevated by PGl/sub 2/. Since inhibition of cAMP is not a prerequisite for platelet activation, the mechanism of potentiation of succinate remains undefined. Lithium has also been shown to inhibit adenylate cyclase in PGl/sub 2/-pretreated platelets. Lithium, however, can also inhibit inositol phosphate (InsP) phosphatase and lead to an accumulation of InsP. In human platelets, lithium also enhanced the thrombin-induced accumulation of (/sup 3/H)inositol-labelled inositol trisphosphate (InsP/sub 3/), and inositol bisphosphate (InsP/sub 2/). One hour after thrombin addition, all 3 inositol phosphates returned to near basal levels. In the presence of lithium, while labelled InsP/sub 2/ and InsP/sub 3/ returned to their respective basal levels, the InsP level remained elevated, consistent with the known inhibitory effect of lithium on InsP phosphatase. In thrombin-stimulated platelets prelabeled with (/sup 32/P)phosphate, lithium led to a decrease in labelled phosphatidylinositol 4-phosphate (PtdIns4P) as well as an enhanced production of labelled lysophosphatidylinositol, suggesting multiple effects of lithium on platelet phosphoinositide metabolism. These observed effects, however, occurred too slowly to be the mechanism by which lithium potentiated agonist-induced platelet activation. To study the agonist-receptor interaction, the effect of the specific, high affinity thrombin inhibitor, hirudin, on thrombin-induced accumulation of (/sup 3/H)inositol-labelled inositol phosphates was studied.

• Research Organization: State Univ. of New York, Stony Brook (USA). Health Science Center
• OSTI ID: 6974541
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADENYLIC ACID
ALKALI METALS
AMP
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD PLATELETS
BODY FLUIDS
CARBOXYLIC ACIDS
CHEMICAL ACTIVATION
COAGULANTS
CYCLASES
DAYS LIVING RADIOISOTOPES
DICARBOXYLIC ACIDS
DRUGS
ELEMENTS
ENZYME INHIBITORS
ENZYMES
ESTERASES
ESTERS
HEMATOLOGIC AGENTS
HEMOSTATICS
HYDROLASES
INHIBITION
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LIGHT NUCLEI
LIPIDS
LITHIUM
LYASES
MATERIALS
MEMBRANE PROTEINS
METALS
NUCLEI
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PEPTIDE HYDROLASES
PHOSPHATASES
PHOSPHOLIPIDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RESPONSE MODIFYING FACTORS
SERINE PROTEINASES
SUCCINIC ACID
THROMBIN
TRACER TECHNIQUES
TRITIUM COMPOUNDS