Inhibition of human platelet aggregation by dihydropyrano- and dihydrofuranocoumarins, a new class of cAMP-phosphodiesterase inhibitors

Ole Thastrup; J B Knudsen; J Lemmich; K Winther

Inhibition of human platelet aggregation by dihydropyrano- and dihydrofuranocoumarins, a new class of cAMP-phosphodiesterase inhibitors

Ole Thastrup, J B Knudsen, J Lemmich, K Winther

22 Citations (Scopus)

Abstract

Certain esters of dihydropyranocoumarin and dihydrofuranocoumarin alcohols have previously been shown to inhibit the cAMP-phosphodiesterase from bovine heart. We now report that these naturally occurring coumarins inhibit the high affinity (Km = 1.1 microM) cAMP-phosphodiesterase from human platelets with activities that closely correlate with those obtained using phosphodiesterase from bovine heart tissue. Additionally the coumarins inhibit the aggregation of human platelets induced with ADP, adrenaline and collagen with activities comparable to those of dipyridamole. A lack of significant correlation between these metabolic and functional activities indicates that there exist, besides cAMP-phosphodiesterase inhibition, additional mechanisms of action for the platelet aggregation inhibitory effect of dihydropyrano- and dihydrofuranocoumarins.

Original language	English
Journal	Biochemical Pharmacology
Volume	34
Issue number	12
Pages (from-to)	2137-40
Number of pages	4
ISSN	0006-2952
Publication status	Published - 1985

Keywords

3',5'-Cyclic-AMP Phosphodiesterases
Adenosine Diphosphate
Coumarins
Furans
Humans
Kinetics
Platelet Aggregation
Pyrans

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title = "Inhibition of human platelet aggregation by dihydropyrano- and dihydrofuranocoumarins, a new class of cAMP-phosphodiesterase inhibitors",

abstract = "Certain esters of dihydropyranocoumarin and dihydrofuranocoumarin alcohols have previously been shown to inhibit the cAMP-phosphodiesterase from bovine heart. We now report that these naturally occurring coumarins inhibit the high affinity (Km = 1.1 microM) cAMP-phosphodiesterase from human platelets with activities that closely correlate with those obtained using phosphodiesterase from bovine heart tissue. Additionally the coumarins inhibit the aggregation of human platelets induced with ADP, adrenaline and collagen with activities comparable to those of dipyridamole. A lack of significant correlation between these metabolic and functional activities indicates that there exist, besides cAMP-phosphodiesterase inhibition, additional mechanisms of action for the platelet aggregation inhibitory effect of dihydropyrano- and dihydrofuranocoumarins.",

keywords = "3',5'-Cyclic-AMP Phosphodiesterases, Adenosine Diphosphate, Coumarins, Furans, Humans, Kinetics, Platelet Aggregation, Pyrans",

author = "Ole Thastrup and Knudsen, {J B} and J Lemmich and K Winther",

year = "1985",

language = "English",

volume = "34",

pages = "2137--40",

journal = "Biochemical Pharmacology",

issn = "0006-2952",

publisher = "Elsevier",

number = "12",

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TY - JOUR

T1 - Inhibition of human platelet aggregation by dihydropyrano- and dihydrofuranocoumarins, a new class of cAMP-phosphodiesterase inhibitors

AU - Thastrup, Ole

AU - Knudsen, J B

AU - Lemmich, J

AU - Winther, K

PY - 1985

Y1 - 1985

N2 - Certain esters of dihydropyranocoumarin and dihydrofuranocoumarin alcohols have previously been shown to inhibit the cAMP-phosphodiesterase from bovine heart. We now report that these naturally occurring coumarins inhibit the high affinity (Km = 1.1 microM) cAMP-phosphodiesterase from human platelets with activities that closely correlate with those obtained using phosphodiesterase from bovine heart tissue. Additionally the coumarins inhibit the aggregation of human platelets induced with ADP, adrenaline and collagen with activities comparable to those of dipyridamole. A lack of significant correlation between these metabolic and functional activities indicates that there exist, besides cAMP-phosphodiesterase inhibition, additional mechanisms of action for the platelet aggregation inhibitory effect of dihydropyrano- and dihydrofuranocoumarins.

AB - Certain esters of dihydropyranocoumarin and dihydrofuranocoumarin alcohols have previously been shown to inhibit the cAMP-phosphodiesterase from bovine heart. We now report that these naturally occurring coumarins inhibit the high affinity (Km = 1.1 microM) cAMP-phosphodiesterase from human platelets with activities that closely correlate with those obtained using phosphodiesterase from bovine heart tissue. Additionally the coumarins inhibit the aggregation of human platelets induced with ADP, adrenaline and collagen with activities comparable to those of dipyridamole. A lack of significant correlation between these metabolic and functional activities indicates that there exist, besides cAMP-phosphodiesterase inhibition, additional mechanisms of action for the platelet aggregation inhibitory effect of dihydropyrano- and dihydrofuranocoumarins.

KW - 3',5'-Cyclic-AMP Phosphodiesterases

KW - Adenosine Diphosphate

KW - Coumarins

KW - Furans

KW - Humans

KW - Kinetics

KW - Platelet Aggregation

KW - Pyrans

M3 - Journal article

C2 - 2988567

SN - 0006-2952

VL - 34

SP - 2137

EP - 2140

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

IS - 12

ER -

Inhibition of human platelet aggregation by dihydropyrano- and dihydrofuranocoumarins, a new class of cAMP-phosphodiesterase inhibitors

Abstract

Keywords

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