The bradykinin analog RMP-7 increases intracellular free calcium levels in rat brain microvascular endothelial cells

J Pharmacol Exp Ther. 1994 Oct;271(1):229-37.


The vasoactive peptide bradykinin is believed to cause increased vascular permeability by the activation of B2 receptors on the vascular endothelium. A bradykinin analog, H-Arg-Pro-Hyp-Gly-Thi-Ser-Pro-4-Me-Tyr(psi CH2NH)-Arg-OH (RMP-7), was designed and it was proposed that it might increase cerebrovascular permeability by activating B2 receptors on brain microvasculature. In this report, the effects of RMP-7 and related peptides on bradykinin receptor-induced calcium signaling were examined in rat brain microvascular endothelial (RBME) cultures. RBME cells are responsive to bradykinin and exhibit specific [3H]-bradykinin binding, with Scatchard analysis indicating a major class of sites with a Kd of 3.9 +/- 1.4 nM and a minor class of higher affinity sites (Kd approximately 33 pM). RMP-7 displaces a significant component of specific [3H]-bradykinin binding from RBME cells; RMP-10, and RMP-7 diastereomer with a D-amino acid substitution in the number 9 position, does not. [3H]-bradykinin binding to RBME cells is not displaced by desArg9-bradykinin, which indicates that neither class of sites is a B1 bradykinin receptor. RMP-7 induces an increase in intracellular free calcium levels in RBME cells. The time course, magnitude and concentration dependence of RMP-7-induced calcium signaling is similar to that induced by bradykinin in RBME and other endothelial cells. Compared with RMP-7, RMP-10 is at least 1000 times less potent. However, the level of contamination by RMP-7 in the RMP-12 preparation accounts for its activity, an indication that both the RMP-10 and RMP-12 diastereomers are essentially inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blood-Brain Barrier
  • Bradykinin / analogs & derivatives*
  • Bradykinin / metabolism
  • Bradykinin / pharmacology
  • Brain / blood supply
  • Brain / metabolism*
  • Calcium / metabolism*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / metabolism*
  • Microcirculation / metabolism
  • Molecular Sequence Data
  • Permeability
  • Rats


  • RMP 7
  • Bradykinin
  • Calcium