In:
Biological Chemistry, Walter de Gruyter GmbH, Vol. 397, No. 4 ( 2016-04-1), p. 305-314
Abstract:
Bradykinin (BK) is a nonapeptide important for several physiological processes such as vasodilatation, increase in vascular permeability and release of inflammatory mediators. BK performs its actions by coupling to and activating the B 2 receptor, a family A G-protein coupled receptor. Using a strategy which allows systematical monitoring of BK R 1 and R 9 residues and B 2 receptor acidic residues Glu 5.35(226) and Asp 6.58(298) , our study aims at clarifying the BK interaction profile with the B 2 receptor [receptor residue numbers are normalized according to Ballesteros and Weinstein, Methods Neurosci. 25 (1995), pp. 366–428) followed by receptor sequence numbering in brackets]. N- and C-terminal analogs of BK (-A 1 , -G 1 , -K 1 , -E 1 and BK-A 9 ) were tested against wild type B 2 , Glu 5.35(226) Ala and Asp 6.58(298) Ala B 2 mutant receptors for their affinity and capability to elicit responses by mechanical recordings of isolated mice stomach fundus, measuring intracellular calcium mobilization, and competitive fluorimetric binding assays. BK showed 2- and 15-fold decreased potency for Glu 5.35(226) and Asp 6.58(298) B 2 mutant receptors, respectively. In B 2 -Glu 5.35(226) Ala BK analogs showed milder reduction in evaluated parameters. On the other hand, in the B 2 -Asp 6.58(298) Ala mutant, no N-terminal analog was able to elicit any response. However, the BK-A 9 analog presented higher affinity parameters than BK in the latter mutant. These findings provide enough support for defining a novel interaction role of BK-R 9 and Asp 6.58(298) receptor residues.
Type of Medium:
Online Resource
ISSN:
1437-4315
,
1431-6730
DOI:
10.1515/hsz-2015-0221
Language:
Unknown
Publisher:
Walter de Gruyter GmbH
Publication Date:
2016
detail.hit.zdb_id:
1466062-3
SSG:
12
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