The bradykinin B2-receptor in human decidua.
Bacterial infection of the amniotic cavity is one of the most frequent causes of preterm delivery. Bacterial products activate a network of autocrine and paracrine mediators in fetal membranes and decidua, with prostaglandins finally inducing contractions of the myometrium. Bradykinin and its B2-receptor (B2R) seem to be part of this network. In cultured decidua-derived cells, bradykinin stimulates the release of arachidonic acid, interleukin-6 (IL-6), and interleukin-8 (IL-8). These effects are prevented by the specific B2R antagonist Hoe 140. Using a pooled antiserum against peptide sequences of the B2R protein, the receptor can be visualized immunocytochemically. The cells contain mRNA for the B2R, as shown by reverse transcriptase polymerase chain reaction (RT-PCR). Binding studies reveal specific and saturable binding sites for bradykinin with characteristics of the B2R. Binding of bradykinin to the cells is enhanced by the inflammatory mediator interleukin-1beta. In summary, human decidua-derived cells express the B2R, its expression is upregulated in response to interleukin-1beta, and bradykinin stimulates the secretion of further mediators by these cells. Thus, bradykinin and the B2R could play a central role in decidual activation. If so, B2R antagonists would add to established tocolytic therapies that are applied together with antibiotics in cases of chorioamnionitis at low gestational age.
Buchinger
P
P
I. Frauenklinik, Klinikum Innenstadt, Ludwig-Maximilians-Universität, München, Germany.
Rehbock
J
J
D016718:Arachidonic Acid / Q000378:metabolism; D001667:Binding, Competitive / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002250:Carbon Radioisotopes; D018929:Cell Culture Techniques; D003656:Decidua / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D011247:Pregnancy; D012333:RNA, Messenger; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics / Q000378:metabolism*
D065168:Bradykinin Receptor Antagonists; D002250:Carbon Radioisotopes; D007375:Interleukin-1; D012333:RNA, Messenger; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D016718:Arachidonic Acid; C065679:icatibant; D001920:Bradykinin