Covalent complexes of albumin with serotonin, ketanserin and lysergic acid antagonize the activity of serotonin in human platelets

Journal Article · Sat Dec 31 23:00:00 EST 1988 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(89)90565-1· OSTI ID:6257650

VanderBerg, S R; Gonias, S L

Covalent conjugates of bovine serum albumin (BSA) and 5-HT, ketanserin or d-lysergic acid were synthesized and characterized by polyacrylamide gel electrophoresis, whole blood clearance experiments in mice and aggregation studies with human platelets. Using the standard synthesis procedure, each mol of BSA bound 13.4 mol of (/sup 3/H)5-HT. Derivatization did not cause significant protein aggregation as determined by electrophoresis. All three conjugates antagonized the ability of 5-HT to amplify aggregation caused by low concentrations of ADP. The antagonist activity of each conjugate was concentration dependent; 2.6 ..mu..M 5-HT-BSA completely inhibited the aggregation caused by 13 ..mu..M 5-HT. None of the BSA drug conjugates, including 5-HT-BSA, amplified platelet aggregation caused by ADP in the absence of 5-HT. Aggregation by ristocetin, collagen, epinephrine or ADP alone was not significantly affected by the conjugates. Whole blood elimination experiments in mice demonstrated that the three conjugates and underivatized BSA are equally stable in the circulation. These prototypic 5-HT drug-protein conjugates may be useful for probing 5-HT/sub 2/ receptor-ligand interactions in human platelets.

• Research Organization: Univ. of Virginia Health Sciences Center, Charlottesville (USA)
• OSTI ID: 6257650
• Journal Information: Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 44:23; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADP
ALBUMINS
ALKALOIDS
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD COAGULATION
BLOOD PLATELETS
BLOOD-PLASMA CLEARANCE
BODY FLUIDS
CARBOXYLIC ACIDS
CATTLE
CHEMICAL COMPOSITION
CLEARANCE
COMPLEXES
COVALENCE
DOMESTIC ANIMALS
DRUGS
ELECTROPHORESIS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LYSERGIC ACID
MAMMALS
MAN
MATERIALS
MEMBRANE PROTEINS
MICE
NEUROREGULATORS
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PRIMATES
PROTEINS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
RECEPTORS
RODENTS
RUMINANTS
SEROTONIN
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TRYPTAMINES
VERTEBRATES