Altered cellular signalling and decreased platelet sensitivity to adenosine in insulin-dependent diabetic patients with proliferative retinopathy.
Platelets from patients with insulin-dependent diabetes with proliferative retinopathy showed the same reactivity to ADP as those from control subjects. Responsiveness of platelets to the aggregation inhibitor adenosine and to the analogue N-ethylcarboxamidoadenosine was decreased in diabetes. In contrast, responsiveness to the anti-aggregatory effects of prostaglandin I2 was not significantly altered in diabetes. Platelets from diabetic patients exhibited decreased formation of cyclic AMP in response to N-ethylcarboxamidoadenosine compared with those from control subjects. In contrast, when adenylyl cyclase was stimulated by prostaglandin I2 or by forskolin, no differences in cyclic AMP formation were observed between control and diabetic platelets. Diabetes was associated with an apparent loss of high-affinity binding of [3H]N-ethylcarboxamidoadenosine to platelet membranes. Possible mechanisms that could contribute to this diabetes-induced change in signalling through the platelet A2 adenosine receptor are discussed.
Department of Medicine, University College and Middlesex School of Medicine, Sir Jules Thorn Institute, Middlesex Hospital, London, U.K.
J A
JA
Gasser
M B
MB
Cooper
K C
KC
Tan
E D
ED
Saggerson
D J
DJ
Betteridge
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D001665:Binding Sites; D001792:Blood Platelets / Q000187:drug effects*; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000097:blood / Q000150:complications / Q000378:metabolism*; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D011983:Receptors, Purinergic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D011983:Receptors, Purinergic; D005576:Colforsin; D019830:Adenosine-5'-(N-ethylcarboxamide); D000244:Adenosine Diphosphate; D011464:Epoprostenol; D019204:GTP-Binding Proteins; D000241:Adenosine