2024-03-28T22:15:28Z
https://niigata-u.repo.nii.ac.jp/oai
oai:niigata-u.repo.nii.ac.jp:00016949
2022-12-15T03:48:24Z
453:456
471:537:538:1114
トロンボキサンA_2による血小板活性化機構 : トロンボキサン不応症における解析から
トロンボキサンA_2による血小板活性化機構 : トロンボキサン不応症における解析から
Pathogenetic Analysis of a Platelet Disorder Characterized by the Absence of Thromboxane A_2-Induced Platelet Aggregation
布施, 一郎
platelets
thromboxane A_2(TXA_2) receptor
defective TXA_2-induced platelet aggregation
G protein
phospholipase C
point mutation
血小板
トロンボキサンA_2受容体
トロンボキサン不応症
G蛋白
遺伝子解析
A patient with a mild bleeding disorder whose platelets responded defectively to thromboxane A_2 (TXA_2) was identified, and the mechanism of this dysfunction was analyzed. The platelets were defective in aggregation and release reaction in response to synthetic TXA_2 mimetic (STA_2). When the platelet TXA_2 receptor was examined with both a [^<125>I]-labeled derivative of a TXA_2 receptor antagonist ([^<125>I]-PTAOH) and [^3H]-labeled TXA_2 agonist ([^3H]U-46619), the equilibrium dissociation rate constants(Kd)and the maximal concentrations of binding sites (Bmax) of the platelets to both ligands were within normal ranges, suggesting that the binding capacity of their TXA_2 receptor was normal. STA_2 could not induce IP3 formation and intracellular Ca^<2+> mobilization, whereas these responses to thrombin were within normal ranges. GTP ase activity was also decreased when the patient's platelet membrane was challenged with STA_2. Furthermore, we identified a single amino acid substitution (Arg^<60>→Leu) in the first cytoplasmic loop of the patient's platelet TXA_2 receptor. The mutant receptor expressed in Chinese hamster ovary cells showed decreased TXA_2-induced second messenger formation despite its normal ligand binding affinities. These results suggest that the Arg^<60> to Leu mutation is responsible for the disorder and that this region could also comprise an important functional element for interaction with G protein linked to PLC.
新潟医学会
1997-11
jpn
departmental bulletin paper
http://hdl.handle.net/10191/45512
https://niigata-u.repo.nii.ac.jp/records/16949
AN00182415
00290440
新潟医学会雑誌
新潟医学会雑誌
111
11
676
682
https://niigata-u.repo.nii.ac.jp/record/16949/files/111(11)_676-682.pdf
application/pdf
1.1 MB
2019-08-08