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Proinflammatory Peptides in Relation to Other Inflammatory Mediators
Published in Sami I. Said, Proinflammatory and Antiinflammatory Peptides, 2020
Pierangelo Geppetti, Costanza Emanueli, Michela Figini, Domenico Regoli
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).
The development of chronic pain
Published in Nan Stalker, Pain Control, 2018
There is also evidence that during chronic inflammation a new type of bradykinin receptor acts upon the nociceptive nerves. The appearance of the additional bradykinin receptor may be related to the development of the long-lasting sensitivity of the nociceptors that is a characteristic of severe chronic pain and which makes it so difficult to treat.
Stimulus-Secretion Coupling: Receptors
Published in Stephen W. Carmichael, Susan L. Stoddard, The Adrenal Medulla 1986 - 1988, 2017
Stephen W. Carmichael, Susan L. Stoddard
Using tritiated bradykinin, Kozlowski, Rosser and Hall (1988) identified binding sites in PC12 cells. The binding characteristics paralleled those of the B2 bradykinin receptor. Exposure to nerve growth factor significantly increased the number of bradykinin binding sites, but other characteristics of the binding remained unchanged.
The therapeutic relevance of the Kallikrein-Kinin axis in SARS-cov-2-induced vascular pathology
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Dorsa Sohaei, Morley Hollenberg, Sok-Ja Janket, Eleftherios P. Diamandis, Gennady Poda, Ioannis Prassas
Binding of SARS-CoV-2 to ACE2 not only downregulates ACE2 expression but also alters its catalytic activity, which in turn alters the ACE2-dependent regulation of the plasma kallikrein-kinin system (KKS) (Figure 2) [65,66]. The KKS produces bradykinin via proteolytic cleavage of the high-molecular-weight kininogen (HMWK or HK) by plasma kallikrein (KLK1B) or low-molecular-weight kininogen (LMWK) by tissue kallikrein (KLK1) [67]. Bradykinin is an acute-phase inflammatory hormone-like molecule [68] whose aberrant activity is physiologically controlled by ACE2 [67,69]. SARS-CoV-2-mediated ACE2 downregulation and modification of its activity can lead to aberrant bradykinin accumulation during the early stages of COVID-19. In turn, increased bradykinin can activate pro-inflammatory processes itself, driving endothelial permeability and causing vasodilating effects via bradykinin receptor 2 (BKB2R) activation. Bradykinin can also be processed further by carboxypeptidase N to produce DR9-bradykinin, which acts through bradykinin receptor 1 (BKB1R) to transmit pro-inflammatory signals [70,71]. This interplay between ACE2, the renin-angiotensin system (RAS), and the plasma KKS has been portrayed as generating a “bradykinin storm” that drives disease pathology in the setting of COVID-19 [71].
Natural history of COVID-19 and therapeutic options
Published in Expert Review of Clinical Immunology, 2020
Philippe Gautret, Matthieu Million, Pierre-André Jarrot, Laurence Camoin-Jau, Philippe Colson, Florence Fenollar, Marc Leone, Bernard La Scola, Christian Devaux, Jean Yves Gaubert, Jean-Louis Mege, Joana Vitte, Cléa Melenotte, Jean-Marc Rolain, Philippe Parola, Jean-Christophe Lagier, Philippe Brouqui, Didier Raoult
ACE2 belongs to the family of angiotensin-converting enzymes (ACE) zinc metallopeptidases. Its 170 kDa related ACE protein is also widely distributed and converts the inactive decapeptide, angiotensin (Ang) I to the active vasoconstrictor octapeptide Ang II and lead to the degradation of bradykinin [91,92]. It has recently been hypothesized that the release of bradykinin, a nine amino acid peptide [Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg] with vasoactive function generated when high-molecular weight kininogen (HMWK) is cleaved from plasma-kallikrein, may play a role in the lung problems observed in COVID-19 patients by causing vascular leakage into the lung spaces by signaling through bradykinin receptors (BKB1, BKB2) [93]. Suppression of ACE2 by SARS-CoV-2 might impair the ACE2-mediated hydrolysis of des-Arg9-bradykinin that binds to BKB1.
A rare presentation of angioedema with isolated retropharyngeal and supraglottic involvement
Published in Journal of Community Hospital Internal Medicine Perspectives, 2019
As the exact mechanism of ACE inhibitor induced angioedema is not established, management focuses on discontinuation of ACE inhibitor and supportive care rather than treatment with targeted reversal agents. While efficacy of epinephrine and antihistaminergic medication is not established in ACE inhibitor induced angioedema, the consensus is to initiate these therapies in patients with signs of respiratory compromise due to inability to rule out an allergic/anaphylactic reaction [7,9]. Airway assessment with direct fiberoptic visualization is recommended in the setting of oropharyngeal involvement, followed by intubation of cricothyrotomy if airway obstruction is present [7]. Corticosteroids are also used to reduce swelling and inflammation throughout the hospital admission, though there is no consensus for post discharge steroid usage [7,9]. The usage of bradykinin receptor antagonists is indicated in acute attacks of hereditary angioedema and hence these agents have been trialed in ACE inhibitor induced angioedema [21,22]. These studies have shown such agents to be inefficacious and hence their use is controversial among patients with ACE inhibitor induced angioedema [21,22].