Calcitonin Gene-Related Peptide Inhibits Human Platelet Aggregation

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Calcitonin gene-related peptide (CGRP) is a potent vasodilator in humans. CGRP receptors have also been found in various tissues other than blood vessels, such as the central nervous system, kidney, and heart. However, Iittle is known about the effects of CGRP on human platelets. We investigated the effect of CGRP (human α type) on platelet aggregation in 21 healthy subjects (9 men and 12 women, mean age 54.6 years). CGRP inhibited platelet aggregation in vitro in 19 of the subjects (90.5%) in a dose-dependent manner with 50% inhibitory doses of 1.6 μmol/L and 1.1 μmol/L for aggregation induced by epinephrine and collagen, respectively. 125I-labeled CGRP bound specifically to intact platelets. The dissociation constant (Kd) was 61.9±17.7 pmol and the maximum number of binding sites (Bmax) was 6.4±3.9 pmol/109 platelets. The CGRP analogue (8-37)CGRP, but not calcitonin, inhibited the binding of 125I-CGRP to platelets. CGRP (5 μmol/L), but not (8-37)CGRP or calcitonin, increased the platelet cyclic AMP (cAMP) concentration by 31.7 ±3.6%. Thus, CGRP inhibits platelet aggregation via a specific receptor and by increasing the platelet cAMP concentration. CGRP may play a role in the modulation of platelet function in humans. (Jpn Circ J 1996; 60: 797-804)

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