Premium
Decreased sensitivity to adenosine in platelets from patients with familial hypercholesterolaemia—a change reversed by cholestyramine treatment
Author(s) -
GASSER J. A.,
COOPER M. B.,
TAN K. C. B.,
SAGGERSON E. D.,
BETTERIDGE D. J.
Publication year - 1993
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1993.tb00734.x
Subject(s) - cholestyramine , medicine , endocrinology , platelet , adenosine , forskolin , adenylyl cyclase , chemistry , prostaglandin , cholesterol , receptor
. Platelet‐rich plasma was obtained from patients with untreated heterozygous familial hypercholesterolaemia (FH), from FH patients treated with cholestyramine and from control subjects. Responsiveness of platelets to the aggregation inhibitors adenosine, its analogue N‐ethylcarboxamidoadeno‐sine (NECA) and prostaglandin 1 2 was decreased in FH. Patients on cholestyramine therapy showed normal responsiveness to adenosine and NECA. There were only minor changes in the binding of [ 3 H]NECA to high‐affinity binding sites on platelet membranes from untreated FH or cholestyramine‐treated FH patients. The initial rate of cyclic AMP formation in response to a high concentration of NECA was severely decreased in platelets from FH patients. By contrast, the rate of cyclic AMP formation in response to forskolin or a high concentration of prostaglandin 12 was unchanged. These data point to a defect in the coupling of the platelet A 2 adenosine receptor to adenylyl cyclase in untreated FH patients.