scholarly journals Ecotin-Like ISP ofL. majorPromastigotes Fine-Tunes Macrophage Phagocytosis by Limiting the Pericellular Release of Bradykinin from Surface-Bound Kininogens: A Survival Strategy Based on the Silencing of Proinflammatory G-Protein Coupled Kinin B2and B1Receptors

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Erik Svensjö ◽  
Larissa Nogueira de Almeida ◽  
Lucas Vellasco ◽  
Luiz Juliano ◽  
Julio Scharfstein
Keyword(s):  
G Protein ◽  
Leishmania Major ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Kinin System ◽  
Enzymatic Assays ◽  
Macrophage Phagocytosis ◽  
Plasma Leakage ◽  
Kallikrein Kinin System ◽  
G Protein Coupled

Inhibitors of serine peptidases (ISPs) expressed byLeishmania majorenhance intracellular parasitism in macrophages by targeting neutrophil elastase (NE), a serine protease that couples phagocytosis to the prooxidative TLR4/PKR pathway. Here we investigated the functional interplay between ISP-expressingL. majorand the kallikrein-kinin system (KKS). Enzymatic assays showed that NE inhibitor or recombinant ISP-2 inhibited KKS activation in human plasma activated by dextran sulfate. Intravital microscopy in the hamster cheek pouch showed that topically appliedL. majorpromastigotes (WT andΔisp2/3mutants) potently induced plasma leakage through the activation of bradykinin B2receptors (B2R). Next, using mAbs against kininogen domains, we showed that these BK-precursor proteins are sequestered byL. majorpromastigotes, being expressed at higher % in theΔisp2/3mutant population. Strikingly, analysis of the role of kinin pathway in the phagocytic uptake ofL. majorrevealed that antagonists of B2R or B1R reversed the upregulated uptake ofΔisp2/3mutants without inhibiting macrophage internalization of WTL. major. Collectively, our results suggest thatL. majorISP-2 fine-tunes macrophage phagocytosis by inhibiting the pericellular release of proinflammatory kinins from surface bound kininogens. Ongoing studies should clarify whetherL. majorISP-2 subverts TLR4/PKR-dependent prooxidative responses of macrophages by preventing activation of G-protein coupled B2R/B1R.

scholarly journals Kinins and Their Receptors as Potential Therapeutic Targets in Retinal Pathologies

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1913
Author(s):  
Rahmeh Othman ◽  
Gael Cagnone ◽  
Jean-Sébastien Joyal ◽  
Elvire Vaucher ◽  
Réjean Couture
Keyword(s):  
Renin Angiotensin System ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Kinin System ◽  
Physiological Processes ◽  
Kinin Receptors ◽  
Age Related ◽  
Kallikrein Kinin System ◽  
Retinal Pathologies ◽  
G Protein Coupled

The kallikrein-kinin system (KKS) contributes to retinal inflammation and neovascularization, notably in diabetic retinopathy (DR) and neovascular age-related macular degeneration (AMD). Bradykinin type 1 (B1R) and type 2 (B2R) receptors are G-protein-coupled receptors that sense and mediate the effects of kinins. While B2R is constitutively expressed and regulates a plethora of physiological processes, B1R is almost undetectable under physiological conditions and contributes to pathological inflammation. Several KKS components (kininogens, tissue and plasma kallikreins, and kinin receptors) are overexpressed in human and animal models of retinal diseases, and their inhibition, particularly B1R, reduces inflammation and pathological neovascularization. In this review, we provide an overview of the KKS with emphasis on kinin receptors in the healthy retina and their detrimental roles in DR and AMD. We highlight the crosstalk between the KKS and the renin–angiotensin system (RAS), which is known to be detrimental in ocular pathologies. Targeting the KKS, particularly the B1R, is a promising therapy in retinal diseases, and B1R may represent an effector of the detrimental effects of RAS (Ang II-AT1R).

scholarly journals Preconditioning of the response to ischemia/reperfusion-induced plasma leakage in hamster cheek pouch microcirculation

Clinics ◽  
2012 ◽  
Vol 67 (8) ◽  
pp. 923-929 ◽  
Author(s):  
FG Conceicao ◽  
CM Conde ◽  
E Svensjo ◽  
DA Bottino ◽  
E Bouskela
Keyword(s):  
Ischemia Reperfusion ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Plasma Leakage

A compendium of G-protein–coupled receptors and cyclic nucleotide regulation of adipose tissue metabolism and energy expenditure

2020 ◽  
Vol 134 (5) ◽  
pp. 473-512 ◽  
Author(s):  
Ryan P. Ceddia ◽  
Sheila Collins
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Signaling Pathways ◽  
G Protein ◽  
Uncoupling Protein ◽  
Beige Adipocytes ◽  
Nucleotide Regulation ◽  
Ucp1 Expression ◽  
Thermogenic Adipocytes ◽  
G Protein Coupled

Abstract With the ever-increasing burden of obesity and Type 2 diabetes, it is generally acknowledged that there remains a need for developing new therapeutics. One potential mechanism to combat obesity is to raise energy expenditure via increasing the amount of uncoupled respiration from the mitochondria-rich brown and beige adipocytes. With the recent appreciation of thermogenic adipocytes in humans, much effort is being made to elucidate the signaling pathways that regulate the browning of adipose tissue. In this review, we focus on the ligand–receptor signaling pathways that influence the cyclic nucleotides, cAMP and cGMP, in adipocytes. We chose to focus on G-protein–coupled receptor (GPCR), guanylyl cyclase and phosphodiesterase regulation of adipocytes because they are the targets of a large proportion of all currently available therapeutics. Furthermore, there is a large overlap in their signaling pathways, as signaling events that raise cAMP or cGMP generally increase adipocyte lipolysis and cause changes that are commonly referred to as browning: increasing mitochondrial biogenesis, uncoupling protein 1 (UCP1) expression and respiration.

Vanadium compounds cause activation of G protein-coupled receptor signaling

2020 ◽  
Author(s):  
Debbie C. Crans ◽  
Duaa Althumairy ◽  
Heide Murakami ◽  
B. George Barisas ◽  
Deborah Roess
Keyword(s):  
G Protein ◽  
Receptor Signaling ◽  
G Protein Coupled Receptor ◽  
Vanadium Compounds ◽  
G Protein Coupled
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