Geiger J, Hönig-Liedl P, Schanzenbächer P, Walter U
Medizinische Universitätsklinik, Institut für Klinische Biochemie und Pathobiochemie, Würzburg, Germany.
Eur J Pharmacol. 1998 Jun 19;351(2):235-46. doi: 10.1016/s0014-2999(98)00305-7.
Human platelets express adenosine 5'-diphosphate (ADP)-specific purinoceptors of the P2X and P2Y receptor superfamily, but their structure, diversity, and precise pharmacological profile is not well understood. Here, functional assays with intact platelets and well-characterized nucleotide derivatives were performed in order to characterize the ligand specificity of these platelet-specific purinoceptors. For the signalling pathways investigated (aggregation, rapid Ca2+-influx, desensitization of Ca2+-influx, Ca2+-mobilization, inhibition of adenylyl cyclase), significant differences in ligand specificity were demonstrated. ADP activated all purinoceptors of human platelets, while adenosine 5'-triphosphate (ATP) was a weak agonist for the P2X receptor and an antagonist for the P2Y receptors. The ADP-receptor pathway-antagonist ticlopidine inhibited ADP-evoked aggregation and adenylyl cyclase inhibition but did not affect platelet purinoceptors associated with Ca2+-influx and Ca2+-mobilization. These results indicate the presence of three distinct ADP-selective purinoceptors on human platelets.
人类血小板表达P2X和P2Y受体超家族的腺苷5'-二磷酸（ADP）特异性嘌呤受体，但其结构、多样性和精确的药理学特性尚未完全明确。在此，利用完整血小板和特征明确的核苷酸衍生物进行功能测定，以表征这些血小板特异性嘌呤受体的配体特异性。对于所研究的信号通路（聚集、快速Ca2+内流、Ca2+内流脱敏、Ca2+动员、腺苷酸环化酶抑制），配体特异性存在显著差异。ADP激活了人类血小板的所有嘌呤受体，而腺苷5'-三磷酸（ATP）是P2X受体的弱激动剂，是P2Y受体的拮抗剂。ADP受体途径拮抗剂噻氯匹定抑制ADP诱导的聚集和腺苷酸环化酶抑制，但不影响与Ca2+内流和Ca2+动员相关的血小板嘌呤受体。这些结果表明人类血小板上存在三种不同的ADP选择性嘌呤受体。
