DECREASED SENSITIVITY TO ADENOSINE IN PLATELETS FROM PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA - A CHANGE REVERSED BY CHOLESTYRAMINE TREATMENT

Platelet-rich plasma was obtained from patients with untreated heteroz ygous familial hypercholesterolaemia (FH), from FH patients treated wi th cholestyramine and from control subjects. Responsiveness of platele ts to the aggregation inhibitors adenosine, its analogue N-ethylcarbox amidoadenosine (NECA) and prostaglandin I-2 was decreased in FH. Patie nts on cholestyramine therapy showed normal responsiveness to adenosin e and NECA. There were only minor changes in the binding of [H-3]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 de creased in platelets from FH patients. By contrast, the rate of cyclic AMP formation in response to forskolin or a high concentration of pro staglandin I-2 was unchanged. These data point to a defect in the coup ling of the platelet A(2) adenosine receptor to adenylyl cyclase in un treated FH patients.