EVIDENCE FOR THE FORMATION OF ENDOTHELIN BY LYSED RED-BLOOD-CELLS FROM ENDOGENOUS PRECURSOR

被引:14
作者
TIPPLER, B [1 ]
HERBST, C [1 ]
SIMMET, T [1 ]
机构
[1] RUHR UNIV BOCHUM, DEPT PHARMACOL & TOXICOL, D-44801 BOCHUM, GERMANY
关键词
ENDOTHELIN-1; RED BLOOD CELL; STAPHYLOCOCCAL ALPHA-TOXIN; PHOSPHORAMIDON; PEPSTATIN A; CHYMOSTATIN; LEUPEPTIN;
D O I
10.1016/0014-2999(94)90273-9
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The release of endothelin from various blood cell fractions was investigated. Human as well as rat blood cell fractions homogenized by sonification were incubated in buffer for up to 60 min. Neither in platelet nor leukocyte homogenates from either species could immunoreactive endothelin be detected. In contrast, homogenates of red blood cells from both species showed a rapid and time-dependent rise of immunoreactive endothelin levels, reaching a peak at 15 min and decreasing thereafter. However, at time point 0 no immunoreactive endothelin could be detected. Reverse phase high performance liquid chromatography showed immunoreactive endothelin to consist of endothelin-1 as well as big endothelin-1. The release of immunoreactive endothelin in human and rat homogenates was concentration-dependently inhibited by the protease inhibitors, leupeptin, phosphoramidon, chymostatin and pepstatin A in order of increasing potency. Intact red blood cells did not incorporate [I-125]endothelin-1 nor did they transform exogenous big endothelin-1 to endothelin-1. However, haemolysis of red blood cells with hypotonic saline (0.2%) or incubation with pore-forming staphylococcal alpha-toxin induced the release of immunoreactive endothelin into the buffer samples. Thus, apart from the indirect vasoconstrictor, haemoglobin, red blood cells can also liberate the direct vasoconstrictor, endothelin, a finding expected to be of considerable pathophysiological significance.
引用
收藏
页码:131 / 139
页数:9
相关论文
共 38 条
[11]   FREE HEMOGLOBIN INTERFERES WITH DETECTION OF ENDOTHELIN PEPTIDES [J].
HEMSEN, A ;
LUNDBERG, JM .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 189 (02) :777-781
[12]   ISOLATION AND CHARACTERIZATION OF A NOVEL ENDOGENOUS INHIBITOR OF THE PROTEASOME [J].
LI, XC ;
GU, MZ ;
ETLINGER, JD .
BIOCHEMISTRY, 1991, 30 (40) :9709-9715
[13]   THE MECHANISMS BY WHICH HEMOGLOBIN INHIBITS THE RELAXATION OF RABBIT AORTA INDUCED BY NITROVASODILATORS, NITRIC-OXIDE, OR BOVINE RETRACTOR PENIS INHIBITORY FACTOR [J].
MARTIN, W ;
SMITH, JA ;
WHITE, DG .
BRITISH JOURNAL OF PHARMACOLOGY, 1986, 89 (03) :563-571
[14]  
MASAOKA H, 1989, LANCET, V2, P1402
[15]   PHOSPHORAMIDON PREVENTS CEREBRAL VASOSPASM FOLLOWING SUBARACHNOID HEMORRHAGE IN DOGS - THE RELATIONSHIP TO ENDOTHELIN-1 LEVELS IN THE CEREBROSPINAL-FLUID [J].
MATSUMURA, Y ;
IKEGAWA, R ;
SUZUKI, Y ;
TAKAOKA, M ;
UCHIDA, T ;
KIDO, H ;
SHINYAMA, H ;
HAYASHI, K ;
WATANABE, M ;
MORIMOTO, S .
LIFE SCIENCES, 1991, 49 (11) :841-848
[16]   THE HIGH MOLECULAR-WEIGHT MULTICATALYTIC PROTEINASE, MACROPAIN, EXISTS IN A LATENT FORM IN HUMAN-ERYTHROCYTES [J].
MCGUIRE, MJ ;
MCCULLOUGH, ML ;
CROALL, DE ;
DEMARTINO, GN .
BIOCHIMICA ET BIOPHYSICA ACTA, 1989, 995 (02) :181-186
[17]   PURIFICATION AND CHARACTERIZATION OF A HIGH-MOLECULAR-WEIGHT PROTEINASE (MACROPAIN) FROM HUMAN-ERYTHROCYTES [J].
MCGUIRE, MJ ;
DEMARTINO, GN .
BIOCHIMICA ET BIOPHYSICA ACTA, 1986, 873 (02) :279-289
[18]   INVITRO AND INVIVO ACTIVITY OF CHYMOTRYPSIN-ACTIVATED BIG ENDOTHELIN (PORCINE 1-40) [J].
MCMAHON, EG ;
FOK, KF ;
MOORE, WM ;
SMITH, CE ;
SIEGEL, NR ;
TRAPANI, AJ .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 161 (02) :406-413
[19]   HUMAN ERYTHROCYTE MULTICATALYTIC PROTEINASE - ACTIVATION AND BINDING TO SULFATED GALACTOSYLCERAMIDES AND LACTOSYLCERAMIDES [J].
OHKUBO, I ;
GASA, S ;
NAMIKAWA, C ;
MAKITA, A ;
SASAKI, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 174 (03) :1133-1140
[20]   OXYHEMOGLOBIN STIMULATION OF ENDOTHELIN PRODUCTION IN CULTURED ENDOTHELIAL-CELLS [J].
OHLSTEIN, EH ;
STORER, BL .
JOURNAL OF NEUROSURGERY, 1992, 77 (02) :274-278