Year: 1977
Type: conference-paper
Abstract: Induction of the platelet response to ADP and many other agonists is accompanied by reduction from basal level of cyclic AMP (cAMP) . The Squibb compound 22536 (9-(tetrahydro-2-furyl)-adenine), an inhibitor of lung adenylate cyclase (Harris et al. Fed. Proc. 34:617, 1975), reverses the inhibition of platelet function and prevents elevation of platelet cAMP by drugs that stimulate adenylate cyclase, including PGE1, PGD2 and adenosine. It reduces basal and PGE1-or NaF-stimulated adenylate cyclase activity and enhances the inhibition of basal activity induced by epinephrine. SQ22536 reduces basal cAMP levels but does not initiate the release reaction or platelet aggregation. It does, however, increase the effect on cAMP of platelet stimulants such as ADP and epinephrine and enhances serotonin release and aggregation induced by ADP, epinephrine, collagen, thrombin, arachidonic acid, endoperoxide PGG2, centrifugation, and rewarming after chilling. Enhancement of platelet activity by SQ22536 in citrated PRP is demonstrable only over a narrow range of agonist concentrations where primary aggregation without release is transformed to complete aggregation with release. SQ22536 does not enhance platelet stimulation by vasopressin, serotonin, or the calcium ionophore Lilly A23187; these substances activate platelets without lowering cyclic AMP, unlike the stimuli listed above. In heparinized PRP, ADP-induced platelet aggregation is accompanied by serotonin release in the presence (but not in the absence) of SQ22536. These results suggest that reduction of cAMP may be involved in the initiation of release in platelets conditioned by a variety of phenomena, including primary aggregation.
Source: Thrombosis and Haemostasis
Institutions: Harvard University, University of Cambridge
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2946639830