Characterisation of kinin receptors on the human isolated umbilical artery

Abstract

The aim of this study was to determine the kinin responses on human umbilical artery (HUA) and to characterise the kinin receptors present on this tissue. The HUA was found to constrict in response to both the B 2 receptor agonist, bradykinin (BK), and the B 1 receptor agonist, des-Arg 9 -BK. The presence of indomethacin (2·79 µM) was found to have no significant effect on the responses to BK and des-Arg 9 -BK. The presence of the B 2 receptor antagonist, HOE-140 (+2·79 µM indomethacin), resulted in a concentration-related rightward displacement of the concentration-effect curves to BK. The antagonism of the constrictor responses to BK by HOE-140 was found to be competitive (pA 2 =7·5). The responses to BK were not significantly affected by the B 1 receptor antagonist des-Arg 9 (leu 8 )BK. The presence of des-Arg 9 (leu 8 )BK (+2·79 µM indomethacin) resulted in a concentrationrelated rightward displacement of the concentration-effect curve to des-Arg 9 -BK. The antagonism of the response to des-Arg 9 -BK by des-Arg 9 (leu 8 )BK was found to be competitive (pA 2 =5·9). The responses to des-Arg 9 -BK were not significantly affected by HOE-140. The results of the present study suggest that the products of the cyclooxygenase pathway are not involved in the kinin constrictor response on HUA and indicate the presence of B 1 and B 2 receptors on this tissue.

Vasomotor Effects of Acetylcholine, Bradykinin, Noradrenaline, 5-Hydroxytryptamine, Histamine and Angiotensin II on the Mouse Basilar Artery

“…The calculated pA 2 value of HOE140 is 7.53, which is identical to the value for the human isolated umbilical artery, i.e. 7.50 [1]. …”

In vivo protein-DNA interactions at the kinin B1 receptor gene promoter: No modification on interleukin-1 beta or lipopolysaccharide induction

“…1 were transiently transfected into three different cell types: human lung fibroblast cells , primary cultures of human SMCs, and human embryonic kidney 293 cells (HEK-293). The first two cell types are known to endogenously express functional B 1 Rs [Menke et al, 1994;Abbas et al, 1998]. Due to variations in transfection efficiency, it is difficult to make an accurate comparison of the basal activities of the same construct in different cells.…”

“…Recently, several studies based on transient transfection experiments of promoter fragments fused to a reporter gene have indicated the presence of positive and negative control regions in the human B 1 R gene promoter region [Yang et al, 1998] and the putative implication of the nuclear factor-kappa B (NF-B) in the IL-1␤ upregulation of the B 1 R gene expression [Ni et al, 1998;Schanstra et al, 1998;Zhou et al, 1998]. As potential features of a strongly regulated gene were found, we have conducted a high resolution in vivo footprinting analysis of the human B 1 R gene promoter region in three human cell types: IMR-90 cells and primary cultures of human umbilical artery SMCs (both of which represent a relevant model for the regulated expression of the human B 1 R gene in functional studies Menke et al, 1994;Abbas et al, 1998]) and in the human embryonic kidney (HEK-293) cell line (which does not exhibit endogenous B 1 R binding [Yang et al, 1998] and was used for comparison).…”

Potentiation of des-Arg9-Kallidin-Induced Vasoconstrictor Responses by Metallopeptidase Inhibition in Isolated Human Umbilical Artery

“…The only work to date that proposed the presence of BKB 1 receptors mediating contraction in HUA was carried out in presence of indomethacin, with low oxygen tension in Krebs' media and with unusually low obtained maximum responses (Abbas et al, 1998). In our study, CRCs to DAKD obtained in the presence of triple enzymatic inhibition yielded a maximum effect approximately 2-fold and a potency approximately 30-fold higher when compared with those obtained in control HUA rings.…”