1998 Fiscal Year Final Research Report Summary

Pathogenesis of a bleeding disorder characterized by platelet unresponsiveness to thromboxane A_2

Research Project

Project/Area Number	09671101
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Hematology
Research Institution	Niigata University
Principal Investigator	FUSE Ichiro Niigata University School of Medicine, Associate Professor, 医学部, 助教授 (90242429)
Co-Investigator(Kenkyū-buntansha)	HANAWA Haruo Niigata University Hospital, Assistant, 医学部附属病院, 助手 (40282983) FUKUKAWA Tatsuo Niigata University Hospital, Associate Professor, 医学部附属病院, 助教授 (00272849)
Project Period (FY)	1997 – 1998
Keywords	Platelets / Thromboxane A_2 / Receptor / Platelet unresponsiveness to thrombxane A_2
Research Abstract	We investigated the mutation of the thromboxane A_2 (TXA_2) receptor in six patients with platelet unresponsiveness to TXA_2, and found that all of the patients patients have the same abnormality of the TXR (Arg^<60> to Leu), although four patients are homozygous and two patients are heterozygous for this mutation. However, in the latter patients, TXA_2-induced IP_3 formation and Ca^<2+> mobilization were within normal limilts. These results suggest that this mutation is the only abnormality which has been found in this platelet disorder, and that, in patients with heterozygous for this mutation, the mutant type TXR suppress the wild-type receptor mediated platelet aggregation by the mechanism independent of phospholipase C.