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Induction of uPA release in human peripheral blood lymphocytes by [deamino-Cys^l,D-Arg⁸]-vasopressin (dDAVP)

¹Department of Plastic and Reconstructive Surgery and ³Environmental Biochemistry, Graduate School of Medicine, Chiba University, Chiba 260-8670; and ²Division of Clinical Research, Sakura National Hospital, Sakura 285-8765, Japan

Submitted 24 March 2003 ; accepted in final form 4 June 2004

[deamino-Cys^l,D-Arg⁸]-vasopressin (dDAVP), known to be an arginine vasopressin (AVP) V₂ 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 V₂ receptor remain unclarified. Two AVP receptors, V_1a and V₂, 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 V₂ receptor antagonist [Adamantaneacetyl¹,O-Et-D-Tyr²,Val⁴,Aminobutyryl⁶,Arg^8,9]-vasopressin, the dDAVP-induced uPA increase was diminished. In contrast, preincubation with a V₁ receptor antagonist, [-Mercapto-,-cyclopentamethylenepropionyl¹,O-Me-Tyr²,Arg⁸]-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 V₂ receptor-mediated reaction, and also via cross-talk between V₁ and V₂ receptors.

arginine vasopressin; plasminogen activator; urokinase-type plasminogen activator; protease release

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