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Ian Orchard - One of the best experts on this subject based on the ideXlab platform.
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identification and cloning of the Kinin receptor in the chagas disease vector rhodnius prolixus
General and Comparative Endocrinology, 2020Co-Authors: Vishal Sangha, Angela B Lange, Ian OrchardAbstract:Abstract Within invertebrates, the Kinin family of neuropeptides is responsible for the modulation of a host of physiological and behavioural processes. In Rhodnius prolixus, Kinins are primarily responsible for eliciting myotropic effects on various feeding and diuresis-related tissues. Here, the R. prolixus Kinin receptor (RhoprKR) has been identified, cloned and sequenced from the central nervous system (CNS) and hindgut of R. prolixus. Sequence analyses show high similarity and identity between RhoprKR and other cloned invertebrate Kinin receptors. The expression profile of RhoprKR shows the RhoprKR transcript throughout the R. prolixus gut, with highest expression in the hindgut, suggesting a role of Rhopr-Kinins in various aspects of feeding and digestion. RNA interference (RNAi)-mediated knockdown of the RhoprKR transcript resulted in a significant reduction of hindgut contractions in response to Rhopr-Kinin 2 and an Aib-containing Kinin analog. dsRhoprKR- injected insects also consumed a significantly larger meal, suggesting a role of Rhopr-Kinins in satiety.
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physiological effects of biostable Kinin and capa analogs in the chagas disease vector rhodnius prolixus
Insect Biochemistry and Molecular Biology, 2019Co-Authors: Vishal Sangha, Angela B Lange, Ronald J Nachman, Ian OrchardAbstract:Abstract In the Chagas disease vector Rhodnius prolixus, the Kinin and CAPA family of neuropeptides are implicated in feeding and diuresis-related behaviours, with Rhopr-Kinins stimulating contractions of the midgut, salivary glands, and hindgut, and RhoprCAPA-2 functioning as an anti-diuretic hormone. The current study examined the effects of Kinin and CAPA neuropeptides and their analogs on feeding and diuresis, and on hindgut contractions and MT fluid secretion in R. prolixus. The biostable Aib-containing Kinin analog 2139[Φ1]wp-2 was found to have antifeedant effects, and to be more potent than Rhopr-Kinin 2 in stimulating hindgut contractions. The CAPA analog 2129-SP3[Φ3]wp-2 induced the intake of a larger blood meal, and increased the rate of post-prandial rapid diuresis. RhoprCAPA-2, but not its analog, potentiated hindgut contractions induced by Rhopr-Kinin 2. Potentiation was observed with the CAPA analog on 5-HT-stimulated increases in frequency of hindgut contractions, whereas RhoprCAPA-2 inhibited this 5-HT-mediated stimulation. The CAPA analog induced hindgut contractions and prevented the inhibition induced by RhoprCAPA-2 on 5-HT-stimulated MT secretion. These results demonstrate novel interactions between Rhopr-Kinin and RhoprCAPA-2 on the hindgut, possibly influencing post-feeding excretion. The Kinin analog is a potent agonist of the Kinin receptor, and the CAPA analog an antagonist of the CAPA receptor. The use of neuropeptide mimetics is a promising approach to vector control as they can disrupt behaviours, and the effects of these neuropeptide analogs highlight their value as lead compounds, given their ability to interfere with epidemiologically-relevant behaviours.
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the molecular characterization of the Kinin transcript and the physiological effects of Kinins in the blood gorging insect rhodnius prolixus
Peptides, 2014Co-Authors: Garima Bhatt, Rosa Da Silva, Ronald J Nachman, Ian OrchardAbstract:Abstract The dramatic feeding-related activities of the Chagas’ disease vector, Rhodnius prolixus are under the neurohormonal regulation of serotonin and various neuropeptides. One such family of neuropeptides, the insect Kinins, possess diuretic, digestive and myotropic activities in many insects. In this study, we have cloned and examined the spatial expression of the R. prolixus Kinin (Rhopr-Kinin) transcript. In addition, in situ hybridization has been used to map the distribution of neurons expressing the Kinin transcript. Physiological bioassays demonstrate the myostimulatory effects of selected Rhopr-Kinin peptides and also illustrate the augmented responses of hindgut contractions to co-application of Rhopr-Kinin and a R. prolixus diuretic hormone. Two synthetic Kinin analogs have also been examined on the hindgut. These reveal interesting properties including a relatively irreversible effect on hindgut contractions and activity at very low concentrations.
Albert Adam - One of the best experts on this subject based on the ideXlab platform.
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the effect of electronegativity and angiotensin converting enzyme inhibition on the Kinin forming capacity of polyacrylonitrile dialysis membranes
Biomaterials, 2008Co-Authors: Anik Desormeaux, Marie Eve Moreau, Yves Lepage, Jacques Chanard, Albert AdamAbstract:The combination of negatively-charged membranes and angiotensin I-converting enzyme inhibitors (ACEi) evokes hypersensitivity reactions (HSR) during hemodialysis and bradyKinin (BK)-related peptides have been hypothesized as being responsible for these complications. In this study, we tested the effects of neutralizing the membrane electronegativity (zeta potential) of polyacrylonitrile AN69 membranes by coating a polyethyleneimine layer (AN69-ST membranes) over the generation of Kinins induced by blood contact with synthetic membranes. We used minidialyzers with AN69 or AN69-ST membranes in an ex vivo model of plasma and we showed that plasma dialysis with AN69 membranes led to significant BK and des-Arg9-BK release, which was potentiated by ACEi. This Kinin formation was dramatically decreased by AN69-ST membranes, even in the presence of an ACEi, and Kinin recovery in the dialysates was also significantly lower with these membranes. High molecular weight Kininogen and factor XII detection by immunoblotting of the protein layer coating both membranes corroborated the results: binding of these proteins and contact system activation on AN69-ST membranes were reduced. This ex vivo experimental model applied to the plasma, dialysate and dialysis membrane could be used for the characterization of the Kinin-forming capacity of any biomaterial potentially used in vivo in combination with drugs which modulate the pharmacological activity of Kinins.
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the kallikrein Kinin system current and future pharmacological targets
Journal of Pharmacological Sciences, 2005Co-Authors: Marie Eve Moreau, Francois Marceau, Nancy Garbacki, Giuseppe Molinaro, Nancy J Brown, Albert AdamAbstract:Abstract The kallikrein-Kinin system is an endogenous metabolic cascade, triggering of which results in the release of vasoactive Kinins (bradyKinin-related peptides). This complex system includes the precursors of Kinins known as Kininogens and mainly tissue and plasma kallikreins. The pharmacologically active Kinins, which are often considered as either proinflammatory or cardioprotective, are implicated in many physiological and pathological processes. The interest of the various components of this multi-protein system is explained in part by the multiplicity of its pharmacological activities, mediated not only by Kinins and their receptors, but also by their precursors and their activators and the metallopeptidases and the antiproteases that limit their activities. The regulation of this system by serpins and the wide distribution of the different constituents add to the complexity of this system, as well as its multiple relationships with other important metabolic pathways such as the renin-angiotensin, coagulation, or complement pathways. The purpose of this review is to summarize the main properties of this kallikrein-Kinin system and to address the multiple pharmacological interventions that modulate the functions of this system, restraining its proinflammatory effects or potentiating its cardiovascular properties.
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the kallikrein Kininogen Kinin system lessons from the quantification of endogenous Kinins
Peptides, 2000Co-Authors: Charles Blais, Francois Marceau, Jeanlucien Rouleau, Albert AdamAbstract:Abstract The purpose of the present review is to describe the place of endogenous Kinins, mainly bradyKinin (BK) and des-Arg9-BK in the kallikrein-Kininogen-Kinin system, to review and compare the different analytical methods reported for the assessment of endogenous Kinins, to explain the difficulties and the pitfalls for their quantifications in biologic samples and finally to see how the results obtained by these methods could complement and extend the pharmacological evidence of their pathophysiological role.
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Development of digoxigenin-labeled peptide: Application to chemiluminoenzyme immunoassay of bradyKinin in inflamed tissues
Peptides, 1994Co-Authors: Anick Décarie, Guy Drapeau, Jean Closset, Réjean Couture, Albert AdamAbstract:Abstract A new ultrasensitive chemiluminoenzyme immunoassay (CLEIA) using digoxigenin-labeled bradyKinin (BK) as a tracer is proposed to quantify Kinins in tissue samples. Rabbit polyclonal IgGs anti-BK directed against the C- terminal end were used for the immunoconcentration step along with dioxetane derivative for the revelation step. The sensitivity of the assay for BK was 0.1 fmol/ml with ED 50 of 0.78 pmol/ml. This method was applied on extracts of normal and carrageenan-inflamed tissues. The edema produced by the injection of carrageenan in rat hindpaws was associated with a sevenfold increase of immunoreactive Kinins in the inflamed paw extract ( from 0.021 ± 0.007 to 0.141 ± 0.021 pmol/g tissue ; p ), the immunoreactivity corresponded to BK, kallidin, and T-Kinin after HPLC separation. When a mixture of inhibitors of Kininase I (mergepta) and Kininase II (captopril) was coinjected with carrageenan, the carrageenan-induced edema was unaffected but the Kinin tissue content was significantly enhanced ( 0.207 ± 0.003 pmol/g tissue ; p ). However, the Kinin tissue content and the edema response were unaltered by inhibitors given separately. Hence, this highly sensitive assay provides a biochemical evidence that Kinins may act as proinflammatory mediators, and highlights a compensatory increase of Kininase I and II activities in inflamed tissues.
Ronald J Nachman - One of the best experts on this subject based on the ideXlab platform.
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physiological effects of biostable Kinin and capa analogs in the chagas disease vector rhodnius prolixus
Insect Biochemistry and Molecular Biology, 2019Co-Authors: Vishal Sangha, Angela B Lange, Ronald J Nachman, Ian OrchardAbstract:Abstract In the Chagas disease vector Rhodnius prolixus, the Kinin and CAPA family of neuropeptides are implicated in feeding and diuresis-related behaviours, with Rhopr-Kinins stimulating contractions of the midgut, salivary glands, and hindgut, and RhoprCAPA-2 functioning as an anti-diuretic hormone. The current study examined the effects of Kinin and CAPA neuropeptides and their analogs on feeding and diuresis, and on hindgut contractions and MT fluid secretion in R. prolixus. The biostable Aib-containing Kinin analog 2139[Φ1]wp-2 was found to have antifeedant effects, and to be more potent than Rhopr-Kinin 2 in stimulating hindgut contractions. The CAPA analog 2129-SP3[Φ3]wp-2 induced the intake of a larger blood meal, and increased the rate of post-prandial rapid diuresis. RhoprCAPA-2, but not its analog, potentiated hindgut contractions induced by Rhopr-Kinin 2. Potentiation was observed with the CAPA analog on 5-HT-stimulated increases in frequency of hindgut contractions, whereas RhoprCAPA-2 inhibited this 5-HT-mediated stimulation. The CAPA analog induced hindgut contractions and prevented the inhibition induced by RhoprCAPA-2 on 5-HT-stimulated MT secretion. These results demonstrate novel interactions between Rhopr-Kinin and RhoprCAPA-2 on the hindgut, possibly influencing post-feeding excretion. The Kinin analog is a potent agonist of the Kinin receptor, and the CAPA analog an antagonist of the CAPA receptor. The use of neuropeptide mimetics is a promising approach to vector control as they can disrupt behaviours, and the effects of these neuropeptide analogs highlight their value as lead compounds, given their ability to interfere with epidemiologically-relevant behaviours.
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the molecular characterization of the Kinin transcript and the physiological effects of Kinins in the blood gorging insect rhodnius prolixus
Peptides, 2014Co-Authors: Garima Bhatt, Rosa Da Silva, Ronald J Nachman, Ian OrchardAbstract:Abstract The dramatic feeding-related activities of the Chagas’ disease vector, Rhodnius prolixus are under the neurohormonal regulation of serotonin and various neuropeptides. One such family of neuropeptides, the insect Kinins, possess diuretic, digestive and myotropic activities in many insects. In this study, we have cloned and examined the spatial expression of the R. prolixus Kinin (Rhopr-Kinin) transcript. In addition, in situ hybridization has been used to map the distribution of neurons expressing the Kinin transcript. Physiological bioassays demonstrate the myostimulatory effects of selected Rhopr-Kinin peptides and also illustrate the augmented responses of hindgut contractions to co-application of Rhopr-Kinin and a R. prolixus diuretic hormone. Two synthetic Kinin analogs have also been examined on the hindgut. These reveal interesting properties including a relatively irreversible effect on hindgut contractions and activity at very low concentrations.
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antifeedant activity and high mortality in the pea aphid acyrthosiphon pisum hemiptera aphidae induced by biostable insect Kinin analogs
Peptides, 2010Co-Authors: Guy Smagghe, Kamran Mahdian, Pawel Zubrzak, Ronald J NachmanAbstract:The insect Kinins are multifunctional neuropeptides found in a variety of arthropod species, including the pea aphid Acyrthosiphon pisum (Hemiptera: Aphidae). A series of biostable insect Kinin analogs based on the shared C-terminal pentapeptide core region were fed in solutions of artificial diet to the pea aphid over a period of 3 days and evaluated for antifeedant and aphicidal activity. The analogs contained either a,a-disubstituted or b-amino acids in key positions to enhance resistance to tissue-bound peptidases and retain activity in a number of insect Kinin bioassays and/or on expressed receptors. Three of the biostable analogs demonstrated antifeedant activity, with a marked reduction in honeydew formation observed after 1 day, and very high mortality. In contrast, an unmodified, parent insect Kinin and two other analogs containing some of the same structural components that promote biostability are inactive. The most active analog, double Aib analog K-Aib-1 ((Aib)FF(Aib)WGa), featured aphicidal activity calculated at an LC50 of 0.063 nmol/ml (0.048 mg/ml) and an LT50 of 1.68 days, matching the potency of some commercially available aphicides. The mechanism of this activity has yet to be established. The aphicidal activity of the biostable insect Kinin analogs may result from different potential mechanisms as disruption of digestive processes by interfering with gut motility patterns, digestive enzyme release, and/or with fluid cycling in the gut, and also nutrient transport across the gut itself; all processes shown to be regulated by the insect Kinins in other insects. However the mechanism(s) is(are) not yet known. The active insect Kinin analogs represent potential leads in the development of selective, environmentally friendly pest aphid control agents.
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enhanced in vivo activity of peptidase resistant analogs of the insect Kinin neuropeptide family
Peptides, 2002Co-Authors: Ronald J Nachman, Allison Strey, Elwyn Isaac, Nan W Pryor, Juan D Lopez, Jingen Deng, Geoffrey M CoastAbstract:Abstract The diuretic/myotropic insect Kinin neuropeptides, which share the common C-terminal pentapeptide core FX 1 X 2 WG-NH 2 , reveal primary (X 2 -W) and secondary (N-terminal to F) sites of susceptibility to peptidases bound to corn earworm ( H. zea ) Malpighian tubule tissue. Analogs designed to enhance resistance to tissue-bound peptidases, and pure insect neprilysin and ACE, demonstrate markedly enhanced in vivo activity in a weight gain inhibition assay in H. zea , and strong in vivo diuretic activity in the housefly ( M. domestica ). The peptidase-resistant insect Kinin analog pQK(pQ)FF[Aib]WG-NH 2 demonstrates a longer internal residence time in the housefly than the native muscaKinin (MK), and despite a difference of over 4 orders of magnitude in an in vitro Malpighian tubule fluid secretion assay, is equipotent with MK in an in vivo housefly diuretic assay. Aminohexanoic acid (Ahx) is shown to function as a surrogate for N-terminal Lys, while at the same time providing enhanced resistance to aminopeptidase attack. Peptidaese-resistant insect Kinin analogs demonstrate enhanced inhibition of weight gain in larvae of the agriculturally destructive corn earworm moth. Potent peptidase resistant analogs of the insect Kinins, coupled with an increased understanding of related regulatory factors, offer promise in the development of new, environmentally friendly pest insect control measures.
Michael Bader - One of the best experts on this subject based on the ideXlab platform.
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Interactions between carboxypeptidase M and Kinin B1 receptor in endothelial cells
Inflammation Research, 2019Co-Authors: Paola Bianchi Guimarães, Michael Bader, Rafael Filippelli Silva, Carolina Caldas Hoff, Liliam Fernandes, Clovis Ryuichi Nakaie, Jair Ribeiro Chagas, Adriana Karaoglanovic Carmona, Joao Bosco PesqueroAbstract:Introduction Carboxypeptidase M (CPM) is a glycosylphosphatidylinositol anchored enzyme that plays an important role in the kallikrein–Kinin system (KKS). CPM catalytic domain hydrolyzes Arg from C-terminal peptides (i.e., bradyKinin and kallidin), generating des-Arg-Kinins, the agonists of B_1 receptor (B_1R). It is known that CPM and Kinin B_1R are co-localized in the plasma membrane microdomains, where they interact with each other, facilitating receptor signaling. Aims We hypothesized here that this CPM-B_1R interaction could also affect the activity of the enzyme. Methods Thus, in this work, we evaluated the impact of B_1R presence or absence on CPM activity and expression, using primary culture of microvascular endothelial cells from wild-type, Kinin B_1R knockout mice (B _1 ^−/− ), and transgenic rats overexpressing B_1 receptor exclusively in the endothelium. In addition, HEK293T cells, as wells as B _1 ^−/− primary culture of endothelial cells, both transfected with B_1R, were also used. Results CPM expression and activity were downregulated in cells of knockout mice compared to control and this reduction was rescued after B_1R transfection. Cells overexpressing B_1R presented higher levels of CPM mRNA, protein, and activity. This profile was reverted by pre-incubation with the B_1R antagonist, R715, in highly expressing receptor cells. Conclusions Our data show that Kinin B_1R positively modulates both CPM expression and activity, suggesting that CPM-B_1R interaction in membrane microdomains might affect enzyme activity, beyond interfering in receptors signaling. This work highlights the interactions among different components of KKS and contributes to a better understanding of its patho-physiological role.
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neutrophil derived proteinase 3 induces kallikrein independent release of a novel vasoactive Kinin
Journal of Immunology, 2009Co-Authors: Robin Kahn, Thomas Hellmark, L Fredrik M Leeblundberg, Nasrin Akbari, Mihail Todiras, Tor Olofsson, Jorgen Wieslander, Anders Christensson, Kerstin Westman, Michael BaderAbstract:The Kinin-forming pathway is activated on endothelial cells and neutrophils when high-molecular weight Kininogen (HK) is cleaved by plasma kallikrein liberating bradyKinin, a potent mediator of inflammation. Kinins are released during inflammatory conditions such as vasculitis, associated with neutrophil influx around blood vessels. Some patients with vasculitis have elevated plasma levels of neutrophil-derived proteinase 3 (PR3) and anti-PR3 Abs. This study investigated if neutrophil-derived PR3 could induce activation of the Kinin pathway. PR3 incubated with HK, or a synthetic peptide derived from HK, induced breakdown and release of a novel tridecapeptide termed PR3-Kinin, NH 2 -MKRPPGFSPFRSS-COOH, consisting of bradyKinin with two additional amino acids on each terminus. The reaction was specific and inhibited by anti-PR3 and α 1 -antitrypsin. Recombinant wild-type PR3 incubated with HK induced HK breakdown, whereas mutated PR3, lacking enzymatic activity, did not. PR3-Kinin bound to and activated human Kinin B 1 receptors, but did not bind to B 2 receptors, expressed by transfected HEK293 cells in vitro. In human plasma PR3-Kinin was further processed to the B 2 receptor agonist bradyKinin. PR3-Kinin exerted a hypotensive effect in vivo through both B 1 and B 2 receptors as demonstrated using wild-type and B 1 overexpressing rats as well as wild-type and B 2 receptor knockout mice. Neutrophil extracts from vasculitis patients and healthy controls contained comparable amounts of PR3 and induced HK proteolysis, an effect that was abolished when PR3 was immunoadsorbed. Neutrophil-derived PR3 can proteolyze HK and liberate PR3-Kinin, thereby initiating kallikrein-independent activation of the Kinin pathway.
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blockade of bradyKinin receptor b1 but not bradyKinin receptor b2 provides protection from cerebral infarction and brain edema
Stroke, 2009Co-Authors: Madeleine Austinat, Michael Bader, Joao Bosco Pesquero, Stefan Braeuninger, Marc Brede, Guido Stoll, Thomas Renne, Christoph KleinschnitzAbstract:Background and Purpose— Brain edema is detrimental in ischemic stroke and its treatment options are limited. Kinins are proinflammatory peptides that are released during tissue injury. The effects of Kinins are mediated by 2 different receptors (B1 and B2 receptor [B1R and B2R]) and comprise induction of edema formation and release of proinflammatory mediators. Methods— Focal cerebral ischemia was induced in B1R knockout, B2R knockout, and wild-type mice by transient middle cerebral artery occlusion. Infarct volumes were measured by planimetry. Evan’s blue tracer was applied to determine the extent of brain edema. Postischemic inflammation was assessed by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. To analyze the effect of a pharmacological Kinin receptor blockade, B1R and B2R inhibitors were injected. Results— B1R knockout mice developed significantly smaller brain infarctions and less neurological deficits compared to wild-type controls (16.8±4.7 mm3 vs 50.1±9.1 m...
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genetically altered animal models in the kallikrein Kinin system
Biological Chemistry, 2006Co-Authors: Joao Bosco Pesquero, Michael BaderAbstract:: Transgenic and gene-targeting technologies allowing the generation of genetically altered animal models have greatly advanced our understanding of the function of specific genes. This is also true for the kallikrein-Kinin system (KKS), in which some, but not yet all, components have been functionally characterized using such techniques. The first genetically altered animal model for a KKS component was supplied by nature, the brown Norway rat carrying an inactivating mutation in the Kininogen gene. Mice deficient in tissue kallikrein, B1 and B2 receptors, some Kinin-degrading enzymes, and factor XII followed, together with transgenic rat and mouse strains overexpressing tissue kallikrein, B1 and B2 receptors, and degrading enzymes. There are still no animal models with genetic alterations in plasma kallikrein, Kininases I and some other degrading enzymes. The models have confirmed an important role of the KKS in cardiovascular pathology, inflammation, and pain, and have partially elucidated the distinct function of the two receptors. This created the basis for rational decisions concerning the putative use of Kinin receptor agonists and antagonists in therapeutic applications. However, a more thorough analysis of the existing models and the generation of new, more sophisticated transgenic models will be necessary to clarify the still elusive issue as to where and by which mechanisms the Kinins exert their actions.
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the use of Kinin b1 and b2 receptor knockout mice and selective antagonists to characterize the nociceptive responses caused by Kinins at the spinal level
Neuropharmacology, 2002Co-Authors: Juliano Ferreira, Maria M. Campos, Ronaldo C Araujo, Michael Bader, Joao Bosco Pesquero, João B. CalixtoAbstract:Abstract The mechanisms by which Kinins induce hyperalgesia in the spinal cord were investigated by using B1 or B2 knockout mice in conjunction with Kinin selective agonists and antagonists. The i.t. administration of the Kinin B2 receptor agonists, bradyKinin (BK) or Tyr8-BK produced dose-related thermal hyperalgesia evaluated in the hot-plate test. BK-induced hyperalgesia was abolished by the B2 receptor antagonist Hoe 140. The i.t. injection of the Kinin B1 receptor agonists, des-Arg9-bradyKinin (DABK) or des-Arg10-kallidin (DAKD) also caused dose-related thermal hyperalgesia. Different from the B2 agonists, the i.t. injection of DABK or DAKD caused a weak, but prolonged hyperalgesia, an effect that was blocked by the B1 receptor antagonist des-Arg9-[Leu8]-bradyKinin (DALBK). The i.t. injection of BK caused thermal hyperalgesia in wild-type mice (WT) and in the B1 receptor knockout mice (B1R KO), but not in the B2 receptor knockout mice (B2R KO). Similarly, the i.t. injection of DABK elicited thermal hyperalgesia in WT mice, but not in B1R KO mice. However, DABK-induced hyperalgesia was more pronounced in the B2R KO mice when compared with the WT mice. The i.t. injection of Hoe 140 or DALBK inhibited the second phase of formalin (F)-induced nociception. Furthermore, i.t. Hoe 140, but not DALBK, also inhibits the first phase of F response. Finally, the i.t. injection of DALBK, but not of Hoe 140, inhibits the long-term thermal hyperalgesia observed in the ipsilateral and in contralateral paws after intraplantar injection with complete Freund’s adjuvant. These findings provide evidence that Kinins acting at both B1 and B2 receptors at the spinal level exert a critical role in controlling the nociceptive processing mechanisms. Therefore, selective Kinin antagonists against both receptors are of potential interest drugs to treat some pain states.
Vishal Sangha - One of the best experts on this subject based on the ideXlab platform.
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identification and cloning of the Kinin receptor in the chagas disease vector rhodnius prolixus
General and Comparative Endocrinology, 2020Co-Authors: Vishal Sangha, Angela B Lange, Ian OrchardAbstract:Abstract Within invertebrates, the Kinin family of neuropeptides is responsible for the modulation of a host of physiological and behavioural processes. In Rhodnius prolixus, Kinins are primarily responsible for eliciting myotropic effects on various feeding and diuresis-related tissues. Here, the R. prolixus Kinin receptor (RhoprKR) has been identified, cloned and sequenced from the central nervous system (CNS) and hindgut of R. prolixus. Sequence analyses show high similarity and identity between RhoprKR and other cloned invertebrate Kinin receptors. The expression profile of RhoprKR shows the RhoprKR transcript throughout the R. prolixus gut, with highest expression in the hindgut, suggesting a role of Rhopr-Kinins in various aspects of feeding and digestion. RNA interference (RNAi)-mediated knockdown of the RhoprKR transcript resulted in a significant reduction of hindgut contractions in response to Rhopr-Kinin 2 and an Aib-containing Kinin analog. dsRhoprKR- injected insects also consumed a significantly larger meal, suggesting a role of Rhopr-Kinins in satiety.
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physiological effects of biostable Kinin and capa analogs in the chagas disease vector rhodnius prolixus
Insect Biochemistry and Molecular Biology, 2019Co-Authors: Vishal Sangha, Angela B Lange, Ronald J Nachman, Ian OrchardAbstract:Abstract In the Chagas disease vector Rhodnius prolixus, the Kinin and CAPA family of neuropeptides are implicated in feeding and diuresis-related behaviours, with Rhopr-Kinins stimulating contractions of the midgut, salivary glands, and hindgut, and RhoprCAPA-2 functioning as an anti-diuretic hormone. The current study examined the effects of Kinin and CAPA neuropeptides and their analogs on feeding and diuresis, and on hindgut contractions and MT fluid secretion in R. prolixus. The biostable Aib-containing Kinin analog 2139[Φ1]wp-2 was found to have antifeedant effects, and to be more potent than Rhopr-Kinin 2 in stimulating hindgut contractions. The CAPA analog 2129-SP3[Φ3]wp-2 induced the intake of a larger blood meal, and increased the rate of post-prandial rapid diuresis. RhoprCAPA-2, but not its analog, potentiated hindgut contractions induced by Rhopr-Kinin 2. Potentiation was observed with the CAPA analog on 5-HT-stimulated increases in frequency of hindgut contractions, whereas RhoprCAPA-2 inhibited this 5-HT-mediated stimulation. The CAPA analog induced hindgut contractions and prevented the inhibition induced by RhoprCAPA-2 on 5-HT-stimulated MT secretion. These results demonstrate novel interactions between Rhopr-Kinin and RhoprCAPA-2 on the hindgut, possibly influencing post-feeding excretion. The Kinin analog is a potent agonist of the Kinin receptor, and the CAPA analog an antagonist of the CAPA receptor. The use of neuropeptide mimetics is a promising approach to vector control as they can disrupt behaviours, and the effects of these neuropeptide analogs highlight their value as lead compounds, given their ability to interfere with epidemiologically-relevant behaviours.
