Receptors for alpha 2-macroglobulin- and pregnancy zone protein-proteinase complexes in the human placental syncytiotrophoblast.
Receptors for complexes between alpha 2-macroglobulin (alpha 2M) and proteinases (e.g. trypsin) were identified and characterized in the human placenta. The receptors also bound the complex formed between pregnancy zone protein (PZP) and chymotrypsin, although with slightly lower affinity, whereas binding of alpha 2M or PZP in their native forms was negligible. Treatment with methylamine to cleave the internal thiol esters caused an increase in binding affinity of alpha 2M to the level of alpha 2M-trypsin but only a minor increase in the affinity of PZP. Chorionic villi prepared from normal full-term placentae were approximately half occupied by endogenous alpha 2M or PZP complexes. These ligands, as well as prebound 125I-labelled alpha 2M-trypsin, were rapidly removed by the addition of 5 mM EDTA. Binding was similar in villi from eight-week and full-term placentae. Autoradiography showed that labelled alpha 2M-trypsin was associated with the syncytiotrophoblast. The kinetics of 125I-labelled alpha 2M-trypsin binding at 4 degrees C was similar in isolated villi and microvillous membranes. Association was slow, with apparent equilibrium by about 16 h. Dissociation of prebound tracer was slow but markedly accelerated in the presence of unlabelled ligand at a saturating concentration. The concentration-dependence of binding at equilibrium yielded a non-linear Scatchard plot. Most of the binding of ligand at tracer concentration was accounted for by high-affinity receptors with a dissociation constant (Kd) of about 50 pM. The content of high-affinity receptors in one placenta was estimated as approximately 125 pmol, i.e., a significant fraction of the total receptor population in the pregnant woman.
Jensen
P H
PH
Institute of Physiology, University of Aarhus, Denmark.
Moestrup
S K
SK
Sottrup-Jensen
L
L
Petersen
C M
CM
Gliemann
J
J
D002824:Chorionic Villi / Q000378:metabolism; D005260:Female; D006801:Humans; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008566:Membranes / Q000378:metabolism / Q000648:ultrastructure; D010920:Placenta / Q000032:analysis* / Q000378:metabolism / Q000648:ultrastructure; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000032:analysis* / Q000378:metabolism; D014327:Trophoblasts / Q000032:analysis* / Q000378:metabolism / Q000648:ultrastructure; D000511:alpha-Macroglobulins / Q000378:metabolism
D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011257:Pregnancy Proteins; D011971:Receptors, Immunologic; D000511:alpha-Macroglobulins