Binding of endothelin to plasma proteins and tissue receptors: effects on endothelin determination, vasoactivity, and tissue kinetics

FEBS Letters

Löffler, Bernd-Michael²  Watzinger, N.³  Brunner, Friedrich¹  Opie, Lionel H.⁴  Stessel, Heike¹ 

[1] Institut für Pharmakologie und Toxikologie, Universität Graz, Universitätsplatz 2, 8010 Graz, Austria;F. Hoffmann-La Roche, Ltd., Preclinical Research, CH-4002 Basel, Switzerland;Medizinische Universitätsklinik, Universität Graz, A-8036 Graz, Austria;University of Cape Town Medical School, Ischaemic Heart Disease Research Unit, Cape Town, South Africa

关键词: Plasma protein binding;    Endothelin-1;    Big endothelin-1;    Vasoactivity;    Tissue kinetics;    Congestive heart failure;    Myocardial infarction;   

DOI  :  10.1016/0014-5793(95)01017-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In vitro binding of (3-[¹²⁵I]Tyr)-endothelin-1 ([¹²⁵I]ET-1) and (3-[¹²⁵I]Tyr)-big ET-1(1–38) ([¹²⁵I]big ET-1) to plasma proteins of healthy humans, cardiac patients and normotensive and hypertensive rats was investigated by equilibrium dialysis. Binding of both tracers was similar in plasma from healthy humans, patients with congestive heart failure, and following myocardial infarction (∼60%), and marginally higher in rat plasmas (∼70%). Binding of [¹²⁵I]ET-1 to human plasma could be explained by binding to human serum albumin. Endogenous plasma ET-1 levels were ∼9 pg/ml in healthy humans, and ∼12–16 pg/ml in cardiac patients; big ET-1 concentrations were approximately two- to threefold higher. ET-1 bound to plasma protein was partly lost in column extraction. In rat isolated perfused hearts, the coronary dilator and constrictor potency of exogenous free and albumin-bound ET-1 was similar, whereas the kinetics of endogenous ET-1 was impeded by tight binding to ET receptors. The data indicate that binding of ET-1 to plasma proteins is without effect on peptide vasoactivity, but binding to tissue receptors greatly impedes its tissue kinetics.

【 授权许可】

Unknown