Background: Adrenomedullin (ADM) is a hypotensive peptide isolated from human pheo chromocytoma extracts discovered in 1993 using an assay system designed to monitor its ability to increase rat platelet adenosine 3',5'-cyclic monophosphate (cAMP) levels. Physio logical mediators that elevate cAMP levels, such as prostaglandin (PG)E1 and PGI2, have also been shown to inhibit platelet aggregation. Therefore, we have chosen to investigate the effect of ADM, a peptide shown to increase platelet cAMP levels, on human platelet aggregation.
Methods and Results: Platelet-rich plasma prepared from blood donors was incubated with ADM (10-9-10-6 M) for 1 min at 37°C before the addition of a submaximal dose of adeno sine 5'-diphosphate (ADP). ADM did not alter the platelet aggregatory response to ADP. PGE1, a substance known to inhihit ADP-induced human platelet aggregation (10-6 M), however, inhibited ADP-induced platelet aggregation. In addition, the ADM induced a dose-dependent relation in rings of human chorionic arteries.
Conclusions: These data may be interpreted to suggest that human platelets do not possess a functional ADM receptor couple with adenylate cyclase.
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