Ca2+ signalling of kinins in cells expressing rat, mouse and human B1/B2-receptor.

Abstract:

:With respect to functional aspects, the kallikrein-kinin-system can be divided into a plasma kallikrein-kinin-system and a tissue kallikrein-kinin-system. At least four functional kinin peptides act via two different G-protein-coupled receptors, an inducible B1-receptor and a constitutively expressed B2-receptor. B1R and B2R couple to G(q/11) and lead via phospholipase C to Ca2+ mobilization. In humans both, bradykinin and kallidin are agonists on the B2-receptor. In contrast, bradykinin is believed to be the only kinin acting on the B2R in rats and mice. However, recently we have isolated a kallidin-like-peptide from plasma and urine of rats. Until now the kinin ligand-receptor interactions were mainly characterized in binding studies. However, receptor affinity does not inevitably correspond with the intrinsic activity of an agonist. The aim of the present study was to investigate intracellular calcium mobilization to quantify mouse, rat and human B1- and B2-receptor activation by bradykinin, kallidin, des-Arg9-bradykinin, des-Arg10-kallidin, and of the two novel rat kinins, kallidin-like-peptide and des-Arg10-kallidin-like-peptide. In cells stably expressing the human, rat, and mouse B2-receptor, respectively, bradykinin, kallidin, and kallidin-like-peptide were nearly equipotent (EC50, 10(-12)M) at eliciting Ca2+-transients. Their des-Arg-derivatives were 10(3)-fold less potent. In cells expressing B1-receptor the des-Arg derivatives elicited Ca2+-signals at an EC50 in the order of 10(-9)M. Major differences between these peptides could not be observed. Bradykinin, kallidin, and kallidin-like-peptide caused a Ca2+-signal at substantially higher concentrations in the order of 10(-7)M. The data show that des-Arg9-bradykinin, des-Arg10-kallidin, and des-Arg10-kallidin-like-peptide are equipotent agonists at the B1-receptor. Bradykinin, kallidin and kallidin-like-peptide are equipotent agonists at the B2-receptor.

journal_name

Int Immunopharmacol

authors

Zubakova R,Gille A,Faussner A,Hilgenfeldt U

doi

10.1016/j.intimp.2007.10.001

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

276-81

issue

2

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(07)00311-6

journal_volume

8

pub_type

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