嘌呤受体激动剂对中性粒细胞趋化作用的抑制

Inhibition of neutrophil chemotaxis by purinoceptor agonists.

作者信息

Elferink J G, de Koster B M, Boonen G J, de Priester W

机构信息

Departments of Medical Biochemistry, Biology, University of Leiden, The Netherlands.

出版信息

Arch Int Pharmacodyn Ther. 1992 May-Jun;317:93-106.

PMID:1456845

Abstract

Adenine nucleotides inhibited fMet-Leu-Phe-activated chemotaxis by rabbit neutrophils in the micromolar concentration range. The sequence of inhibitory effectiveness was ATP[S] greater than ATP greater than ADP greater than AMP greater than adenosine. In the presence of EDTA, inhibition of chemotaxis by ATP occurred to the same degree as in the presence of Ca2+ (and Mg2+), indicating that neither ectonucleotidases nor Ca2+ fluxes across the plasma membrane are of importance for the inhibitory effect. The inhibitory effect of ATP persisted when the nucleotide was removed after preincubation, before the cells were submitted to chemotaxis. Exposure of neutrophils to ApCpp results in desensitization towards inhibition by ATP. Other nucleoside triphosphates, such as XTP, GTP, ITP, CTP and UTP, also inhibited neutrophil migration. The relative potency of the nucleotides, which are used to discriminate between the subtypes of the P2 purinoceptor, was (at a concentration of 50 microM) ATP greater than ApCpp greater than AppNp greater than MeSATP greater than AppCp. The results suggest that inhibition of neutrophil chemotaxis by purinoceptor agonists is mediated by P2 purinoceptors and that the subtype is different from the P2x or P2y purinoceptor.

摘要

腺嘌呤核苷酸在微摩尔浓度范围内可抑制兔中性粒细胞由N - 甲酰 - 甲硫氨酰 - 亮氨酰 - 苯丙氨酸（fMet - Leu - Phe）激活的趋化作用。抑制效力顺序为：ATP[S]＞ATP＞ADP＞AMP＞腺苷。在存在乙二胺四乙酸（EDTA）的情况下，ATP对趋化作用的抑制程度与存在Ca²⁺（和Mg²⁺）时相同，这表明胞外核苷酸酶和跨质膜的Ca²⁺通量对抑制作用均不重要。在细胞进行趋化作用之前，预孵育后去除核苷酸时，ATP的抑制作用仍然存在。中性粒细胞暴露于ApCpp会导致对ATP抑制作用的脱敏。其他核苷三磷酸，如XTP、GTP、ITP、CTP和UTP，也抑制中性粒细胞迁移。用于区分P2嘌呤受体亚型的核苷酸相对效力（浓度为50 μM时）为：ATP＞ApCpp＞AppNp＞甲基 - 硫代 - ATP（MeSATP）＞AppCp。结果表明，嘌呤受体激动剂对中性粒细胞趋化作用的抑制是由P2嘌呤受体介导的，且该亚型不同于P2x或P2y嘌呤受体。