Bradykinin B1, receptors in human umbilical vein:: pharmacological evidence of up-regulation, and induction by interleukin-1β

Bradykinin B-1 receptor-mediated responses increase as a function of in vitro incubation in the human umbilical vein. When tissues were continuously treated with the protein synthesis inhibitor, cycloheximide, or with the protein trafficking inhibitor, brefeldin A, pEC(50) and maximal response to the selective bradykinin B-1 receptor agonist, des-Arg(9)-bradykinin, were significantly diminished. The anti-inflammatory steroid, dexamethasone, produced a rightward shift of the concentration-response curve to des-Arg(9)-bradykinin, without affecting the maximal response. Furthermore, lipopolysaccharide or recombinant human interleukin-1 beta potentiate the bradykinin B-1-sensitized responses, showing a leftward shift of the concentration-response curve to des-Arg(9)-bradykinin, without modifying the maximal response. On the other hand, bradykinin B-2 receptor-mediated responses were unaffected by continuous exposure to cycloheximide, dexamethasone or lipopolysaccharide. These results provide pharmacological evidence to support the view that the de novo synthesis of bradykinin B-1 receptors is involved in the induction of vascular responses in the human umbilical vein. This up-regulation process seems to be selective for bradykinin B-1 receptors. The inhibitory effect of dexamethasone and the potentiating actions of lipopolysaccharide and exogenous human recombinant interleukin-1 alpha on des-Arg(9)-bradykinin-mediated responses, suggest the possible role of interleukin-1 beta in the bradykinin beta(1) receptor up-regulation phenomenon in human umbilical vein. (C) 1998 Elsevier Science B.V. All rights reserved.