Anagrelide, a potent inhibitor of platelet aggregation, inhibits inositol phosphate generation and elevates cAMP

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5451450

Grove, R I; Euler, C C; Stanton, H C

The effects of the potent platelet aggregation inhibitor, anagrelide (6,7-dichloro-1,5-dihydroimidazo(2,1-6)quinazolin-2(/sup 3/H)-one monohydrochloride; BL-4162A), on polyphosphoinositide metabolism in human platelets was investigated. Anagrelide maximally inhibited the thrombin-stimulated increase in inositol phosphates (IPn) at approximately 3.3 x 10/sup -6/M. The time of incubation required for a maximal response was between 15 and 30 min. Since anagrelide has been reported to inhibit low-Km cAMP phosphodiesterase, the authors compared its ability to inhibit stimulated IPn to that of the well known cAMP phosphodiesterase inhibitor IBMX. Both compounds inhibited IPn similarly except in experiments in which the IP phosphatase inhibitor, lithium chloride, was omitted. In these experiments, anagrelide totally inhibited, while IBMX only partially inhibited, the thrombin-stimulated elevation of IPn. The effect of anagrelide on platelet cyclic nucleotide levels was also measured. After 30 min incubation, concentrations of anagrelide which maximally inhibit aggregation induced a 2-fold increase in cAMP without significantly altering cGMP. These results suggest the mechanism of platelet aggregation inhibition includes an anagrelide-induced elevation of cAMP.

• Research Organization: Bristol-Meyers Pharmaceutical, Evansville, IN
• OSTI ID: 5451450
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMP
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD COAGULATION FACTORS
BLOOD PLATELETS
BODY FLUIDS
CARBOHYDRATES
COAGULANTS
DRUGS
ENZYME INHIBITORS
ENZYMES
ESTERASES
HEMATOLOGIC AGENTS
HEMOSTATICS
HYDROLASES
INHIBITION
INOSITOL
INOSITOLS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MATERIALS
METABOLISM
MONOSACCHARIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PEPTIDE HYDROLASES
PHOSPHATES
PHOSPHORUS COMPOUNDS
SACCHARIDES
SERINE PROTEINASES
THROMBIN
TRACER TECHNIQUES
TRITIUM COMPOUNDS