血小板活化因子特异性受体的种属差异。

Species difference in the specific receptors of platelet activating factor.

作者信息

Hwang S B, Lam M H

出版信息

Biochem Pharmacol. 1986 Dec 15;35(24):4511-8. doi: 10.1016/0006-2952(86)90772-0.

Abstract

Relative potencies of platelet activating factor (PAF) and PAF analogs and several PAF receptor antagonists when inhibiting the [3H]PAF specific binding to human and rabbit platelet membranes and membrane fragments of human lung tissues were compared. In rabbit platelets, L-652,731 was found to be most potent in the list of PAF receptor antagonists with an equilibrium inhibition constant (Ki) of 9.83 (+/- 2.92) X 10(-9) M followed by L-653,150 greater than kadsurenone congruent to Ono-6240 greater than ginkgolide B greater than CV-3988 greater than L-651,142, whereas in human platelets the relative potencies of these PAF receptor antagonists were as follows: Ono-6240 greater than L-653,150 congruent to L-652,731 congruent to kadsurenone greater than ginkgolide B greater than CV-3988 greater than L-651,142. Ono-6240 was the most potent one with a Ki of 4.86 (+/- 1.44) X 10(-8) M which was roughly two times more potent than that in rabbit platelets, whereas the affinity of L-652,731 was about ten times less in human platelets (Ki = 1.03 (+/- 0.15) X 10(-7) M) compared to that in rabbit platelets (Ki = 9.83 (+/- 2.92) X 10(-9) M). These variations between species among PAF antagonists strongly suggest that there exists a species difference at or near the binding site of the receptor of platelet activating factor. The relative potency of these PAF receptor antagonists in human lung membranes differed very little from that in human platelets and was found to be Ono-6240 greater than L-653,150 congruent to kadsurenone congruent to L-652,731 greater than ginkgolide B greater than CV-3988 greater than L-651,142. Even though C16-PAF showed slightly higher potency in human lung, and CV-3988 and Ono-6240 showed slightly lower, the difference was too small to suggest that there is a difference in the PAF receptors between human platelets and human lung tissues.

摘要

比较了血小板活化因子（PAF）及其类似物与几种PAF受体拮抗剂在抑制[3H]PAF与人及兔血小板膜以及人肺组织膜片段特异性结合时的相对效力。在兔血小板中，L-652,731在PAF受体拮抗剂中效力最强，其平衡抑制常数（Ki）为9.83（±2.92）×10⁻⁹ M，其次是L-653,150＞海风藤酮≡Ono-6240＞银杏内酯B＞CV-3988＞L-651,142；而在人血小板中，这些PAF受体拮抗剂的相对效力如下：Ono-6240＞L-653,150≡L-652,731≡海风藤酮＞银杏内酯B＞CV-3988＞L-651,142。Ono-6240效力最强，Ki为4.86（±1.44）×10⁻⁸ M，约为兔血小板中效力的两倍，而L-652,731在人血小板中的亲和力（Ki = 1.03（±0.15）×10⁻⁷ M）相比兔血小板（Ki = 9.83（±2.92）×10⁻⁹ M）约低10倍。PAF拮抗剂在不同物种间的这些差异强烈表明，血小板活化因子受体结合位点处或其附近存在物种差异。这些PAF受体拮抗剂在人肺膜中的相对效力与人血小板中的差异很小，为Ono-6240＞L-653,150≡海风藤酮≡L-652,731＞银杏内酯B＞CV-3988＞L-651,142。尽管C16-PAF在人肺中的效力略高，CV-3988和Ono-6240的效力略低，但差异太小，不足以表明人血小板与人肺组织中的PAF受体存在差异。