Evidence that phospholipid turnover is the signal transducing system coupled to serotonin-S2 receptor sites

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

OSTI ID:6528914

Leysen, J E; De Clerck, F; Van Belle, H; Janssen, P A

Upon stimulation with serotonin of washed human platelets prelabeled with (/sup 32/P)orthophosphate, the authors found an approximately 250% increase in (/sup 32/P)phosphatidic acid (PA) formation, a small decrease in (/sup 32/P)phosphatidylinositol 4,5-bisphosphate, and a concomitant increase in (/sup 32/P)phosphatidylinositol 4-phosphate. Using (/sup 3/H)arachidonate for prelabeling, (/sup 3/H)diacylglycerol accumulated transiently at 10 s after addition of the agonist, (/sup 3/H)PA increased but to a lower extent compared to /sup 32/P-labeled lipid, and the formation of both (/sup 3/H)polyphosphoinositides increased. The serotonin-induced dose-dependent changes in (/sup 32/P)PA correlate with its effect on the changes in slope of aggregation of platelets. The potency of 13 drugs to antagonize the serotonin-induced PA formation closely corresponds to both their potency to inhibit platelet aggregation and their binding affinity for serotonin-S2 receptor sites. It is suggested that at least part of the signal transducing system following activation of the serotonin-S2 receptors involves phospholipase C catalyzed inositol lipid breakdown yielding diacylglycerol which is subsequently phosphorylated to PA.

• OSTI ID: 6528914
• 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
AFFINITY
ALCOHOLS
AMINES
ARACHIDONIC ACID
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD PLATELETS
BODY FLUIDS
CARBOHYDRATES
CARBOXYLESTERASES
CARBOXYLIC ACIDS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYMES
ESTERASES
ESTERS
GLYCEROL
HETEROCYCLIC COMPOUNDS
HYDROLASES
HYDROXY COMPOUNDS
INDOLES
INOSITOL
INOSITOLS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIPASE
LIPIDS
MATERIALS
MONOCARBOXYLIC ACIDS
MONOSACCHARIDES
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
OXYGEN COMPOUNDS
PHOSPHATES
PHOSPHOLIPIDS
PHOSPHORUS COMPOUNDS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
RECEPTORS
SACCHARIDES
SEROTONIN
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TRYPTAMINES