Induction of histamine release from rat mast cells by bradykinin analogues

Vietinghoff, Gabriele; Paegelow, I.; Reißmann, Siegmund

doi:10.1016/s0196-9781(96)00214-8

Cited by 10 publications

(2 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore ring-substituted dehydrophenylalanine analogues were used to estimate the influence of the ring-substitution on the activity. From preceding work with bradykinin agonists and antagonists the necessity of estimating the bioactivity at different organs [9,13,14,15,24] had been established. Thus, the smooth muscle organs rat uterus (RUT), guinea pig ileum (GPI) and guinea pig pulmonary artery (PA) were used.…”

Section: Resultsmentioning

confidence: 99%

Bradykinin antagonists with dehydrophenylalanine analogues at position 5

et al. 1998

Self Cite

View full text Add to dashboard Cite

Continuing the studies on structural requirements of bradykinin antagonists, it has been found that analogues with dehydrophenylalanine (deltaPhe) or its ring-substituted analogues (deltaPhe(X)) at position 5 act as antagonists on guinea pig pulmonary artery, and on guinea pig ileum. Because both organs are considered to be bradykinin B2 receptor tissues, the analogues with deltaPhe or deltaPhe(X) at position 5, but without any replacement at position 7, seem to represent a new structural type of B2 receptor antagonist. All the analogues investigated act as partial antagonists; they inhibit the bradykinin-induced contraction at low concentrations and act as agonists at higher concentrations. Ring substitutions by methyl groups or iodine reduce both the agonistic and antagonistic activity. Only substitution by fluorine gives a high potency. Incorporation of deltaPhe into different representative antagonists with key modifications at position 7 does not enhance the antagonist activity of the basic structures, with one exception. Only the combination of deltaPhe at position 5 with DPhe at position 7 increases the antagonistic potency on guinea pig ileum by about one order of magnitude. Radioligand binding studies indicate the importance of position 5 for the discrimination of B2 receptor subtypes. The binding affinity to the low-affinity binding site (KL) was not significantly changed by replacement of Phe by deltaPhe. In contrast, ring-methylation of deltaPhe results in clearly reduced binding to KL. The affinity to the high-affinity binding site (KH) was almost unchanged by the replacement of Phe in position 5 by deltaPhe, whereas the analogue with 2-methyl-dehydrophenylalanine completely failed to detect the KH-site. The peptides were synthesized on the Wang-resin according to the Fmoc/Bu(t) strategy using Mtr protection for the side chain of Arg. The dehydrophenylalanine analogues were prepared by a strategy involving PyBop couplings of the dipeptide unit Fmoc-Gly-deltaPhe(X)-OH to resin-bound fragments.

show abstract

Section: Resultsmentioning

confidence: 99%

Bradykinin antagonists with dehydrophenylalanine analogues at position 5

et al. 1998

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our results also suggest that these mediators can in turn augment the BK effect, as the three antagonists and B2 antagonist together dramatically blocked BK-induced PE, an effect significantly greater than that of B2 antagonist alone. There is evidence that BK is able to induce the release of CGRP, PGs, and histamine in a variety of tissues and cells [ 9 , 10 , 42 ], and these secondary mediators in turn can cause or enhance inflammation [ 7 , 43 – 45 ]. In comparison, our results show that in 5-HT-stimulated PE, PGs and histamine also play important roles, which is in agreement with our previous studies [ 7 , 46 ], but CGRP is apparently not involved.…”

Section: Discussionmentioning

confidence: 99%

Receptor mediation and nociceptin inhibition of bradykinin-induced plasma extravasation in the knee joint of the rat

et al. 2009

View full text Add to dashboard Cite

Objective and designThe aim was to investigate the signaling mechanisms and regulation of bradykinin (BK)-induced inflammation in rat knee joint.Materials and methodsKnee joints of anesthetized rats were perfused with BK (0.1–1.0 μM), and synovial plasma extravasation (PE) was evaluated by spectrophotometrical measurement of Evans Blue leakage. To examine the signaling pathway, B1 antagonist [des-Arg10]-HOE140 (0.1–1.0 μM) and B2 antagonist HOE140 (0.05–1.0 μM), calcitonin gene-related peptide (CGRP) antagonist CGRP8-37 (0.5–1.0 μM), prostaglandin E2 antagonist AH-6809 (0.1–1.0 μM), and histamine H1 antagonist mepyramine (0.1–1.0 μM) were used. Nociceptin (0.0001–1.0 μM) and antagonist J-113397 were tested for modulation of BK-induced PE. The analyses were compared side-by-side with 5-hydroxytryptamine-induced PE.ResultsBK perfusion dose-dependently induced PE, which was blocked by HOE140, CGRP8-37, AH-6809, and mepyramine. It was also inhibited by nociceptin, which could be reversed by antagonist J-113397. In contrast, 5-hydroxytryptamine-induced PE was biphasically regulated by nociceptin and was not antagonized by CGRP8-37.ConclusionsBK-induced PE is mediated by B2 receptors and may involve CGRP, prostaglandin, and histamine pathways. BK-induced PE is inhibited by nociceptin through the activation of ORL1 receptors. There are differences between BK- and 5-hydroxytryptamine-induced inflammation in signaling and modulation.

show abstract