부산대학교 도서관

Quinonoiddihydropteridine reductase (QDPR) regenerates tetrahydrobiopterin (BH4), which is an essential cofactor for catecholamine and serotonin (5-hydroxytryptamine, 5-HT) biosynthesis. Serotonin is known as an important platelet agonist, but its role under BH4-synthesizing or recycling enzymes deficiency is unknown. In the present study, we evaluated the effect of Qdprgene disruption on platelet aggregation using knockout (Qdpr−/−) mice. Platelet aggregation was monitored by light transmission aggregometry using adenosine diphosphate (ADP) and collagen as agonists. We also assessed how platelet aggregation was modified by 5-HT recovery through supplementation with 5-hydroxytryptophan (5-HTP), a 5-HT precursor, or by blocking the serotonin 5-HT2Areceptor. Platelet aggregation in the Qdpr−/−mice was significantly suppressed in comparison with that in wild-type (Qdpr+/+) mice, particularly at the maintenance phase of aggregation. 5-HT storage was decreased in Qdpr−/−platelets, and 5-HTP supplementation recovered not only the intraplatelet 5-HT levels but also platelet aggregation. In addition, 5-HT signal blockade using sarpogrelate suppressed platelet aggregation in Qdpr+/+mice, and platelets in Qdpr−/−mice were hardly affected. Our results indicate that QDPR deficiency suppresses platelet aggregation by impairing 5-HT biosynthesis in mice.