Further analysis of the upregulation of bradykinin B1 receptors in isolated rabbit aorta by using metabolic inhibitors

Eur J Pharmacol. 1994 Dec 27;271(2-3):551-5. doi: 10.1016/0014-2999(94)90819-2.

Abstract

Kinins exert a contractile effect that develops as a function of the in vitro incubation time with isolated rabbit aorta. This response is mediated via receptors of the bradykinin B1 type and interleukin-1 amplifies this upregulation process. Tissues continuously treated with the protein synthesis inhibitor cycloheximide (71 microM) or with the protein trafficking inhibitor, brefeldin A (18 microM), failed to develop a contractile response to the bradykinin B1 receptor agonist, des-Arg9-bradykinin (1.7 microM) (72-100% inhibition of kinin response recorded at 3 or 6 h), whether or not they were exposed to interleukin-1 beta (290 pM). The protein glycosylation inhibitor tunicamycin exerted a selective and significant, but partial (50-76%), inhibition of des-Arg9-bradykinin-induced responses. The biochemical effect of the metabolic inhibitors on the tissue has been validated in assays involving incorporation of [3H]leucine and of [3H]mannose into protein or glycoprotein fractions, respectively. The modulatory effects of metabolic inhibitors on the responses to kinins of the isolated rabbit aorta support the idea that a de novo formation of membrane bradykinin B1 receptors is the molecular basis of both the spontaneous and the interleukin-1-stimulated upregulation phenomenon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects*
  • Aorta / physiology
  • Bradykinin / analogs & derivatives
  • Bradykinin / pharmacology
  • Brefeldin A
  • Cycloheximide / pharmacology
  • Cyclopentanes / pharmacology
  • In Vitro Techniques
  • Interleukin-1 / pharmacology
  • Phenylalanine / pharmacology
  • Rabbits
  • Receptors, Bradykinin / biosynthesis*
  • Tunicamycin / pharmacology
  • Up-Regulation
  • Vasoconstriction / drug effects

Substances

  • Cyclopentanes
  • Interleukin-1
  • Receptors, Bradykinin
  • Tunicamycin
  • bradykinin, des-Arg(9)-
  • Brefeldin A
  • Phenylalanine
  • Cycloheximide
  • Bradykinin