Bradykinin antagonists in human systems: Correlation between receptor binding, calcium signalling in isolated cells, and functional activity in isolated ileum

Wieczorek, Maciej; Pilyavskaya, Anna; Burkard, Michael; Zuzack, John S.; Jones, Steven W.; Francis, Mary D.; Beckey, Virginia E.; Ross, Sherman; Goodfellow, Val S.; Fitzpatrick, Timothy D.; Marathe, Manoj V.; Gyorkos, Albert; Spruce, Lyle W.; Selig, William M.; Stewart, John M.; Gera, Lajos; Whalley, Eric T.

doi:10.1016/s0006-2952(97)00186-x

Cited by 4 publications

(1 citation statement)

References 27 publications

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“…1997 ) indicate that bradykinin invariably increases cytosolic Ca 2+ – at least partly – by release from intracellular stores via activation of a G protein‐coupled receptor and phosphoinoside phospholipase C. When bradykinin affects smooth muscles directly, contraction is always elicited through this pathway ( Marsh & Hill 1994, Mathis et al . 1996 , Wieczorek et al . 1997 ).…”

Section: Discussionmentioning

confidence: 99%

Bradykinin elevates cytosolic Ca²⁺ concentration in smooth muscle cells isolated from rat duodenum

Wassdal

Larsen

1999

Acta Physiologica Scandinavica

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The effect of bradykinin on the cytosolic Ca2+ concentration were measured in single, Fura-2 loaded, smooth muscle cells isolated from rat duodenum. All cells responded with a Ca2+ signal when exposed to bradykinin. The bradykinin response consisted of an initial Ca2+ spike followed by a plateau. Pre-treatment of single muscle cells with either the phospholipase C blocker U-73122 or thapsigargin, which is a potent inhibitor of the endoplasmic reticulum Ca2+-ATPase, inhibited the response to bradykinin. Pre-treatment of the cells with EGTA or La3+ to inhibit the Ca2+ influx, abolished the response induced by bradykinin. We conclude that bradykinin applied to single smooth muscle cells from rat duodenum, increases cytosolic Ca2+ by emptying intracellular Ca2+ stores, and by contribution from extracellular Ca2+. In contrast to bradykinin-induced response in isolated rat duodenum (a relaxation followed by a contraction), we did not observe a biphasic effect of bradykinin on cytosolic Ca2+ in single muscle cells. Bradykinin may thus cause relaxation of duodenal smooth muscle indirectly through an effect on neighbouring cells as dilatation is brought about by this agent in blood vessels.

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Section: Discussionmentioning

confidence: 99%

Bradykinin elevates cytosolic Ca²⁺ concentration in smooth muscle cells isolated from rat duodenum

Wassdal

Larsen

1999

Acta Physiologica Scandinavica

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MEN16132, a novel potent and selective nonpeptide antagonist for the human bradykinin B2 receptor. In vitro pharmacology and molecular characterization

Cucchi

Meini

Bressan

et al. 2005

European Journal of Pharmacology

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Antagonism of Bradykinin B2 Receptor Prevents Inflammatory Responses in Human Endothelial Cells by Quenching the NF-kB Pathway Activation

et al. 2014

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BackgroundBradykinin (BK) induces angiogenesis by promoting vessel permeability, growth and remodeling. This study aimed to demonstrate that the B2R antagonist, fasitibant, inhibits the BK pro-angiogenic effects.MethodologyWe assesed the ability of fasibitant to antagonize the BK stimulation of cultured human cells (HUVEC) and circulating pro-angiogenic cells (PACs), in producing cell permeability (paracellular flux), migration and pseocapillary formation. The latter parameter was studied in vitro (matrigel assay) and in vivo in mice (matrigel plug) and in rat model of experimental osteoarthritis (OA). We also evaluated NF-κB activation in cultured cells by measuring its nuclear translocation and its downstream effectors such as the proangiogenic ciclooxygenase-2 (COX-2), prostaglandin E-2 and vascular endothelial growth factor (VEGF).Principal findingsHUVEC, exposed to BK (1–10 µM), showed increased permeability, disassembly of adherens and tight-junction, increased cell migration, and pseudocapillaries formation. We observed a significant increase of vessel density in the matrigel assay in mice and in rats OA model. Importantly, B2R stimulation elicited, both in HUVEC and PACs, NF-κB activation, leading to COX-2 overexpression, enhanced prostaglandin E-2 production. and VEGF output. The BK/NF-κB axis, and the ensuing amplification of inflammatory/angiogenic responses were fully prevented by fasitibant as well as by IKK VII, an NF-κB. Inhibitor.ConclusionThis work illustrates the role of the endothelium in the inflammation provoked by the BK/NF-κB axis. It also demonstates that B2R blockade by the antaogonist fasibitant, abolishes both the initial stimulus and its amplification, strongly attenuating the propagation of inflammation.

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Bradykinin antagonists in human systems: Correlation between receptor binding, calcium signalling in isolated cells, and functional activity in isolated ileum

Cited by 4 publications

References 27 publications

Bradykinin elevates cytosolic Ca²⁺ concentration in smooth muscle cells isolated from rat duodenum

Bradykinin elevates cytosolic Ca²⁺ concentration in smooth muscle cells isolated from rat duodenum

MEN16132, a novel potent and selective nonpeptide antagonist for the human bradykinin B2 receptor. In vitro pharmacology and molecular characterization

Antagonism of Bradykinin B2 Receptor Prevents Inflammatory Responses in Human Endothelial Cells by Quenching the NF-kB Pathway Activation

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Bradykinin antagonists in human systems: Correlation between receptor binding, calcium signalling in isolated cells, and functional activity in isolated ileum

Cited by 4 publications

References 27 publications

Bradykinin elevates cytosolic Ca2+ concentration in smooth muscle cells isolated from rat duodenum

Bradykinin elevates cytosolic Ca2+ concentration in smooth muscle cells isolated from rat duodenum

MEN16132, a novel potent and selective nonpeptide antagonist for the human bradykinin B2 receptor. In vitro pharmacology and molecular characterization

Antagonism of Bradykinin B2 Receptor Prevents Inflammatory Responses in Human Endothelial Cells by Quenching the NF-kB Pathway Activation

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Product

Resources

About

Bradykinin elevates cytosolic Ca²⁺ concentration in smooth muscle cells isolated from rat duodenum

Bradykinin elevates cytosolic Ca²⁺ concentration in smooth muscle cells isolated from rat duodenum