Evidence for existence of two distinct bradykinin receptors on rat mesangial cells

Am J Physiol. 1993 Mar;264(3 Pt 2):F548-56. doi: 10.1152/ajprenal.1993.264.3.F548.


We investigated the possible presence of bradykinin (BK) B1 receptor on rat mesangial cells (MC) by binding studies and by the effect of the B1 agonist des-Arg9-BK on intracellular calcium concentration ([Ca2+]i) and DNA synthesis in comparison with the effects of BK. Binding studies demonstrated specific, saturable binding for des-Arg9-[3H]BK inhibited by B1 but not by B2 antagonists. Scatchard analysis revealed a single class of B1 binding site with a maximum density of 15 fmol/mg protein and an affinity of 8.7 +/- 2.4 nM. Saturation and competition studies of 125I-[Tyr0]BK demonstrated the presence of two classes of B2 binding sites [dissociation constant (Kd) = 0.1 and 4 nM, respectively]. On fura-2-loaded adherent MC, both des-Arg9-BK and BK induced a biphasic increase (a transient enhancement followed by a sustained phase) in [Ca2+]i, both in primary culture and in cloned MC. Both the transient and sustained phases of [Ca2+]i induced by des-Arg9-BK were dose dependent, whereas BK induced a transient dose-dependent rise in [Ca2+]i, but the sustained phase remained constant. The increases in [Ca2+]i induced by des-Arg9-BK and BK were specifically abolished by B1 and B2 receptor antagonists, respectively, and showed homologous but not heterologous desensitization. Des-Arg9-BK and BK induced a significant proliferation (tested by cell counting and [3H]thymidine incorporation) of quiescent MC. Furthermore, the effects of des-Arg9-BK and BK were additive on Ca2+ mobilization but not on mitogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Bradykinin / analogs & derivatives
  • Bradykinin / metabolism
  • Bradykinin / pharmacology
  • Calcium / metabolism
  • Cell Division / drug effects
  • Cells, Cultured
  • DNA / biosynthesis
  • Kidney Glomerulus / metabolism*
  • Nifedipine / pharmacology
  • Rats
  • Receptors, Bradykinin
  • Receptors, Neurotransmitter / metabolism*
  • Verapamil / pharmacology


  • Receptors, Bradykinin
  • Receptors, Neurotransmitter
  • bradykinin, des-Arg(9)-
  • DNA
  • Verapamil
  • Nifedipine
  • Bradykinin
  • Calcium