Induction of uPA release in human peripheral blood lymphocytes by [deamino-Cysl,D-Arg8]-vasopressin (dDAVP).
Induction of uPA release in human peripheral blood lymphocytes by [deamino-Cysl,D-Arg8]-vasopressin (dDAVP).
复制标题
DOI：
10.1152/ajpendo.00027.2003
复制
发表时间：
2004-06
期刊：
影响因子：
--
通讯作者：
Y. Yamaguchi;Kenichi Yamada;Toshikazu Suzuki;Yu‐ping Wu;K. Kita;Shunji Takahashi;M. Ichinose;N. Suzuki
中科院分区：
文献类型：
--
作者：
Y. Yamaguchi;Kenichi Yamada;Toshikazu Suzuki;Yu‐ping Wu;K. Kita;Shunji Takahashi;M. Ichinose;N. Suzuki
[脱氨基-Cys（1），d-Arg（8）]-加压素（dDAVP），已知是精氨酸加压素（AVP）V（2）受体激动剂，是一种在输注到人体后增加血浆中纤维蛋白溶解活性水平的药剂。然而，肾外dDAVP反应性V（2）受体增加和精确定位的机制仍不清楚。两种AVP受体V（1a）和V（2）以及相关的催产素（OT）受体在人淋巴细胞中表达。此外，我们发现，从人类志愿者外周淋巴细胞的介质中的纤溶活性增加不到20分钟后dDAVP输注。在体外，在dDAVP存在下孵育淋巴细胞后，在培养基中也检测到增加的活性，在孵育后20 min时最高。与纤溶活性的增加相雅阁，培养基中尿激酶型纤溶酶原激活物（uPA）的水平也增加。然而，有没有显着差异的纤溶酶原激活物抑制剂-1（派-1），前uPA，和组织型纤溶酶原激活物（tPA）的浓度在培养基中dDAVP处理和对照之间。当淋巴细胞与V（2）受体拮抗剂[金刚烷乙酰基（1）、O-Et-d-Tyr（2）、瓦尔（4）、氨基丁酰（6）、Arg（8，9）]-加压素预孵育时，dDAVP诱导的uPA增加减弱。相比之下，在dDAVP处理之前，用V（1）受体拮抗剂[β-巯基-β，β-环戊亚甲基丙酰基（1），O-Me-Tyr（2），Arg（8）]-加压素预孵育，导致培养基中uPA浓度比单独dDAVP处理时增加更大。因此，dDAVP可能通过V（2）受体介导的反应以及V（1）和V（2）受体之间的相互作用诱导人淋巴细胞释放uPA。
[deamino-Cys(l),d-Arg(8)]-vasopressin (dDAVP), known to be an arginine vasopressin (AVP) V(2) receptor agonist, is an agent that increases fibrinolytic activity levels in plasma after its infusion into the human body. However, mechanisms underlying an increase and exact localization of the extrarenal dDAVP-responsive V(2) receptor remain unclarified. Two AVP receptors, V(1a) and V(2), and a related oxytocin (OT) receptor were found to be expressed in human lymphocytes. Furthermore, we found an increase of fibrinolytic activity in the medium of peripheral lymphocytes obtained from human volunteers less than 20 min after dDAVP infusion. The increased activity was also detected in the medium after incubating the lymphocytes in the presence of dDAVP in vitro, being highest at 20 min after the incubation. In accord with the increased fibrinolytic activity, the levels of urokinase-type plasminogen activator (uPA) in the medium were also increased. However, there was no significant difference of plasminogen activator inhibitor-1 (PAI-1), pro-uPA, and tissue-type plasminogen activator (tPA) concentrations in the medium between dDAVP treatment and control. When lymphocytes were preincubated with a V(2) receptor antagonist [Adamantaneacetyl(1),O-Et-d-Tyr(2),Val(4),Aminobutyryl(6),Arg(8,9)]-vasopressin, the dDAVP-induced uPA increase was diminished. In contrast, preincubation with a V(1) receptor antagonist, [beta-Mercapto-beta,beta-cyclopentamethylenepropionyl(1),O-Me-Tyr(2),Arg(8)]-vasopressin, prior to dDAVP treatment resulted in a greater increase of the uPA concentration in the medium than with the dDAVP treatment alone. Thus it was suggested that dDAVP may induce uPA release from human lymphocytes via V(2) receptor-mediated reaction, and also via cross-talk between V(1) and V(2) receptors.