Proinflammatory Peptides in Relation to Other Inflammatory Mediators
Sami I. Said in Proinflammatory and Antiinflammatory Peptides, 2020
Bradykinin is a pleiotropic molecule that interacts with a variety of cells, producing a broad series of biological responses. Inflammatory responses to bradykinin may be mediated by direct activation of bradykinin receptors, usually of the B2 type, on effector cells. However, in-vivo conditions and particularly when bradykinin is administered locally, direct contribution of kinin receptor activation on effector cells is minor, whereas the ability of bradykinin to release different mediators that orchestrate a complex biological response is more evident. Recent studies have also shown that bradykinin may release mediators that exert antiinflammatory action. Thus, the final response to bradykinin reflects the contrasting actions of the different mediators released by this autacoid. One example of these possible interactions is the bronchoconstriction induced by bradykinin in guinea pigs. Bradykinin, if injected intravenously, causes a bronchoconstrictor response that is mediated by prostanoids, and in minor part by an atropine-sensitive cholinergic reflex pathway. If is administered by aerosolization, the constrictor effect of bradykinin is mediated mainly by tachykinin release from sensory nerve endings (57), although in this case also, a minor contribution of cholinergic nerves has been described (57).
Local Regulation of Endothelium-Dependent Responses
Thomas F. Lüscher, Paul M. Vanhoutte in The Endothelium: Modulator of Cardiovascular Function, 2020
Bradykinin is formed in the blood and the kidney upon activation of the kinin system; it contributes to the regulation of the secretion of exocrine glands. Bradykinin causes endothelium-dependent relaxations in many blood vessels including cerebral arteries (Figure 8)167,168,545,610,1360,1390 In cultured endothelial cells obtained from experimental animals, bradykinin stimulates the release of EDRF, which most likely is nitric oxide (see Chapter 4, Figure 4106,186,452,743,947 The receptor on the endothelial cells linked to the release of EDRF belongs to the B2-kinin subtype.1099,1390
Pain
Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella in Essentials of Human Physiology and Pathophysiology for Pharmacy and Allied Health, 2019
The sensitization of nociceptors following tissue damage or inflammation results from a variety of chemicals released or activated in the injured area (see Table 15.1). These substances decrease the threshold for activation of the nociceptors. One such substance that seems to elicit more pain than the others is bradykinin. Activated by enzymes released from damaged cells, bradykinin causes pain by several mechanisms including: Direct activation of A-delta and C fibersAlong with histamine, it contributes to the inflammatory response to tissue injuryPromotes the synthesis and release of prostaglandins from nearby cells.
Relationship between G proteins coupled receptors and tight junctions
Published in Tissue Barriers, 2018
Lorenza González-Mariscal, Arturo Raya-Sandino, Laura González-González, Christian Hernández-Guzmán
Bradykinin is a 9-amino acid peptide generated by the proteolytic cleavage of high-molecular weight kininogen by the enzymes kallikreins, and is degraded by kininases including angiotensin-converting enzyme. Bradykinin dilates blood vessels causing a fall in blood pressure. Bradykinin and its long-lasting analogue labradimil/RPM-7, selective for the G-coupled bradykinin receptor 2 (BR2), induce a higher increase in permeability in the blood-brain tumor barrier than in the BBB. This feature is of utmost therapeutic importance as it allows the delivery of hydrophilic chemotherapeutics,214,215 and virus vectors with killing-genes.216 to brain tumors and not to healthy brain tissue. In brain microvascular endothelial cells BR2 through Gαi inhibits adenylyl cyclase decreasing the expression of cAMP and PKA and through Gαq stimulates PLC to increase intracellular calcium. These changes alter the perijunctional actin cytoskeleton and down-regulates the expression of ZO-1, occludin and claudin-5.217 The increase in blood-brain tumor barrier permeability is also mediated by ROCK activation that induces TJ protein relocalization, stress fibers formation, and MLC and cofilin phosphorylation,218,219 and by a NOS dependent mechanism that induces the translocation to the nucleus of ZONAB transcription factor, which inhibits the promoters of claudin-5 and occludin genes, resulting in a reduced expression of the corresponding TJ proteins.220
Plasma concentrations of tissue kallikrein in normal and preeclamptic pregnancies
Published in Hypertension in Pregnancy, 2020
Chunyan Yuan, Yuyu Yao, Cong Fu, Tianai Rong, Bing Li, Abdlay Carvalho, Chang Liu
Tissue kallikrein (TK) is a serine protease that converts kininogen to the vasoactive peptides bradykinin (3). Bradykinin is a potent vasodilator that plays important roles in controlling vascular tone, local blood flow, electrolyte and glucose transport, pain, inflammation, and vascular permeability (4). The kallikrein-kinin system has a significant role in the regulation of systemic blood pressure (5). Transgenic mice carrying the human TK gene had significantly lower blood pressure (6). TK is significantly reduced in the urine of patients with essential hypertension (7). In addition, clinical studies have shown that the blood pressure of hypertensive patients can be temporarily lowered by oral administration of porcine pancreatic kallikrein (8). These results suggest that TK is involved in blood pressure homeostasis.
Trabecular meshwork ECM remodeling in glaucoma: could RAS be a target?
Published in Expert Opinion on Therapeutic Targets, 2018
It is also important to consider that inhibition of ACE results in accumulation of bradykinin. Tissue bradykinin mediates its actions through B1 and B2 receptors. Between the two, B2 receptors mediate most physiological effects of bradykinin. Expression of both the B1 and B2 receptors has been observed in the anterior segment of human eye including TM [93]. Bradykinin stimulation of B2 receptors promotes MMP-9 secretion from TM cells via ERK1/2 activation, and this is associated with an increase in AH outflow facility [94,95]. One of the studies has shown that bradykinin stimulates activity of plasminogen activator via B2 receptors and this is associated with increased MMP-2 secretion [96]. In this study, the effect of bradykinin on plasminogen activator was shown to be independent of the changes in PAI-1 expression. However, Okada et al. showed that benazepril, an ACEI, but not CGP-48933, an AT1 receptor blocker, decreases PAI-1 expression by renal epithelial cells, both in vivo and in vitro. This effect of benazepril was associated with reduced TGF-β1 expression, increased MMP-9 secretion, and reduced collagen I deposition [97]. Hence, it is likely that the effects of RAS inhibition, in particular ACEI, on ECM remodeling at least partially are mediated through alternate pathways in an Ang receptor-independent manner.
Related Knowledge Centers
- Arteriole
- Inflammation
- Kinin
- Peptide
- Prostacyclin
- Protein
- Nitric Oxide
- Amino Acid
- Endothelium-Derived Hyperpolarizing Factor
- Prostaglandin F2Alpha