Chemotactic activities of vasoactive intestinal peptide, neuropeptide Y and substance P in Leishmania braziliensis

Giammarressi, Michelle; Vanegas, Oriana; Febres, Anthony; Silva-López, Adrián; López, Emilia Díaz; Ponte-Sucre, Alicia

doi:10.1016/j.exppara.2020.108009

Cited by 4 publications

(9 citation statements)

References 27 publications

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“…Of note, CGRP 8-37 by itself but not AM 22-52 , produce a chemorepellent effect. Altogether these results suggest the presence of GPCR receptors or GPCR-like receptor signaling system in Leishmania not homolog to those expressed in vertebrates ( Febres et al., 2018 ; Giammarressi et al., 2020 ; Febres et al., 2021 ).…”

Section: Gpcr Like Signaling Systems In Leishmaniamentioning

confidence: 80%

“…( Díaz and Ponte-Sucre, 2018 ). Leishmania parasites and the cutaneous nervous system roles for successful macrophage-promastigote interaction and initiation of inflammatory processes are pivotal to have one or other result ( Giammarressi et al., 2020 ). The final answer will depend on the response to the received signals, the skin being a key place where these signals are processed to build up a reply, since the skin as an organ, reacts to endogenous and exogenous signals, perceive and integrate environmental stimuli, and reacts.…”

Section: Gpcr Like Signaling Systems In Leishmaniamentioning

confidence: 99%

“…The data presented demonstrates the in vitro effect of sensory [Substance P, SP (10 -8 M), chemoattractant] and autonomic [(Vasoactive Intestinal Peptide, VIP (10 -10 M), and Neuropeptide Y, NPY (10 -9 M), chemorepellent] neuropeptides at physiological levels on parasite taxis. And additionally, the chemorepellent effect of the vasoactive molecules Calcitonin Gene-Related Peptide [(CGRP) (10 -9 and 10 -8 M)] and Adrenomedullin [(AM) (10 -9 to 10 -5 M)] ( Febres et al., 2018 ; Giammarressi et al., 2020 ; Febres et al., 2021 ).…”

Section: Gpcr Like Signaling Systems In Leishmaniamentioning

confidence: 99%

“… Antagonism of CGRP8–37, AM22–52, Anti-RAMP-2, VIP (VIP6-28), NPY (GR2323118) and (D-Pro2, D-Trp7,9]-Substance P, on the chemotactic response elicited by CGRP, AM, VIP, NPY and SP, on L. (V.) braziliensis . ( Febres et al., 2018 , Giammarressi et al., 2020 ; Febres et al, 2021 ). The figure details the chemoattractant or chemorepellent effect (as percentages, see the abscisa) of sensorial and autonomic peptides and their respective antagonist (either alone or in combination with the agonist) and their effect on the migratory response in Leishmania ( V .)…”

Section: Gpcr Like Signaling Systems In Leishmaniamentioning

confidence: 99%

“…Potentially they may induce metabolic activation before the invasion of the macrophages and the dendritic cells (DC). The zoom detail depicts flagellum membrane organization including a scheme of potential transmembrane receptors that may be (NK1, Y1 and VAPC), G-protein (like), CRLR (like) coupled RAMP (1,2) receptors ( Giammarressi et al., 2020 ), and RAC receptors.…”

Section: Ramp or Ramp-like Proteins In Leishmaniamentioning

confidence: 99%

See 4 more Smart Citations

G Protein-Coupled Receptors as Potential Intercellular Communication Mediators in Trypanosomatidae

Díaz

Febres

Giammarresi

et al. 2022

Front. Cell. Infect. Microbiol.

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Detection and transduction of environmental signals, constitute a prerequisite for successful parasite invasion; i.e., Leishmania transmission, survival, pathogenesis and disease manifestation and dissemination, with diverse molecules functioning as inter-cellular signaling ligands. Receptors [i.e., G protein-coupled receptors (GPCRs)] and their associated transduction mechanisms, well conserved through evolution, specialize in this function. However, canonical GPCR-related signal transduction systems have not been described in Leishmania, although orthologs, with reduced domains and function, have been identified in Trypanosomatidae. These inter-cellular communication means seem to be essential for multicellular and unicellular organism’s survival. GPCRs are flexible in their molecular architecture and may interact with the so-called receptor activity-modifying proteins (RAMPs), which modulate their function, changing GPCRs pharmacology, acting as chaperones and regulating signaling and/or trafficking in a receptor-dependent manner. In the skin, vasoactive- and neuro- peptides released in response to the noxious stimuli represented by the insect bite may trigger parasite physiological responses, for example, chemotaxis. For instance, in Leishmania (V.) braziliensis, sensory [Substance P, SP, chemoattractant] and autonomic [Vasoactive Intestinal Peptide, VIP, and Neuropeptide Y, NPY, chemorepellent] neuropeptides at physiological levels stimulate in vitro effects on parasite taxis. VIP and NPY chemotactic effects are impaired by their corresponding receptor antagonists, suggesting that the stimulated responses might be mediated by putative GPCRs (with essential conserved receptor domains); the effect of SP is blocked by [(D-Pro 2, D-Trp7,9]-Substance P (10-6 M)] suggesting that it might be mediated by neurokinin-1 transmembrane receptors. Additionally, vasoactive molecules like Calcitonin Gene-Related Peptide [CGRP] and Adrenomedullin [AM], exert a chemorepellent effect and increase the expression of a 24 kDa band recognized in western blot analysis by (human-)-RAMP-2 antibodies. In-silico search oriented towards GPCRs-like receptors and signaling cascades detected a RAMP-2-aligned sequence corresponding to Leishmania folylpolyglutamate synthase and a RAMP-3 aligned protein, a hypothetical Leishmania protein with yet unknown function, suggesting that in Leishmania, CGRP and AM activities may be modulated by RAMP- (-2) and (-3) homologs. The possible presence of proteins and molecules potentially involved in GPCRs cascades, i.e., RAMPs, signpost conservation of ancient signaling systems associated with responses, fundamental for cell survival, (i.e., taxis and migration) and may constitute an open field for description of pharmacophores against Leishmania parasites.

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Section: Gpcr Like Signaling Systems In Leishmaniamentioning

confidence: 80%

Section: Gpcr Like Signaling Systems In Leishmaniamentioning

confidence: 99%

Section: Gpcr Like Signaling Systems In Leishmaniamentioning

confidence: 99%

Section: Gpcr Like Signaling Systems In Leishmaniamentioning

confidence: 99%

Section: Ramp or Ramp-like Proteins In Leishmaniamentioning

confidence: 99%

See 3 more Smart Citations

G Protein-Coupled Receptors as Potential Intercellular Communication Mediators in Trypanosomatidae

Díaz

Febres

Giammarresi

et al. 2022

Front. Cell. Infect. Microbiol.

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Antimicrobial neuropeptides and their therapeutic potential in vertebrate brain infectious disease

Li,

Chen,

Liu

et al. 2024

Front. Immunol.

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The defense mechanisms of the vertebrate brain against infections are at the forefront of immunological studies. Unlike other body parts, the brain not only fends off pathogenic infections but also minimizes the risk of self-damage from immune cell induced inflammation. Some neuropeptides produced by either nerve or immune cells share remarkable similarities with antimicrobial peptides (AMPs) in terms of size, structure, amino acid composition, amphiphilicity, and net cationic charge. These similarities extend to a wide range of antibacterial activities demonstrated in vitro, effectively protecting nerve tissue from microbial threats. This review systematically examines 12 neuropeptides, pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal peptide (VIP), α-melanocyte stimulating hormone (α-MSH), orexin-B (ORXB), ghrelin, substance P (SP), adrenomedullin (AM), calcitonin-gene related peptide (CGRP), urocortin-II (UCN II), neuropeptide Y (NPY), NDA-1, and catestatin (CST), identified for their antimicrobial properties, summarizing their structural features, antimicrobial effectiveness, and action mechanisms. Importantly, the majority of these antimicrobial neuropeptides (9 out of 12) also possess significant anti-inflammatory properties, potentially playing a key role in preserving immune tolerance in various disorders. However, the connection between this anti-inflammatory property and the brain’s infection defense strategy has rarely been explored. Our review suggests that the combined antimicrobial and anti-inflammatory actions of neuropeptides could be integral to the brain’s defense strategy against pathogens, marking an exciting direction for future research.

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Mammalian Neuropeptides as Modulators of Microbial Infections: Their Dual Role in Defense versus Virulence and Pathogenesis

Augustyniak

Kramarska

Mackiewicz

et al. 2021

IJMS

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The regulation of infection and inflammation by a variety of host peptides may represent an evolutionary failsafe in terms of functional degeneracy and it emphasizes the significance of host defense in survival. Neuropeptides have been demonstrated to have similar antimicrobial activities to conventional antimicrobial peptides with broad-spectrum action against a variety of microorganisms. Neuropeptides display indirect anti-infective capacity via enhancement of the host’s innate and adaptive immune defense mechanisms. However, more recently concerns have been raised that some neuropeptides may have the potential to augment microbial virulence. In this review we discuss the dual role of neuropeptides, perceived as a double-edged sword, with antimicrobial activity against bacteria, fungi, and protozoa but also capable of enhancing virulence and pathogenicity. We review the different ways by which neuropeptides modulate crucial stages of microbial pathogenesis such as adhesion, biofilm formation, invasion, intracellular lifestyle, dissemination, etc., including their anti-infective properties but also detrimental effects. Finally, we provide an overview of the efficacy and therapeutic potential of neuropeptides in murine models of infectious diseases and outline the intrinsic host factors as well as factors related to pathogen adaptation that may influence efficacy.

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Chemotactic activities of vasoactive intestinal peptide, neuropeptide Y and substance P in Leishmania braziliensis

Cited by 4 publications

References 27 publications

G Protein-Coupled Receptors as Potential Intercellular Communication Mediators in Trypanosomatidae

G Protein-Coupled Receptors as Potential Intercellular Communication Mediators in Trypanosomatidae

Antimicrobial neuropeptides and their therapeutic potential in vertebrate brain infectious disease

Mammalian Neuropeptides as Modulators of Microbial Infections: Their Dual Role in Defense versus Virulence and Pathogenesis

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