Alpha2-adrenoceptors in human lymphocytes: Direct characterisation by [3H]yohimbine binding

Titinchi, Saad Jaber; Clark, Barry

doi:10.1016/0006-291x(84)90679-x

Cited by 47 publications

(24 citation statements)

References 22 publications

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“…In contrast to the well-established expression of b-adrenoceptors in lymphocytes (58), only a few studies have postulated, using indirect methods, the presence of a-adrenoceptors in mononuclear peripheral blood cells (10,33,55,56). Their presence has also been suggested, similarly by indirect evidence, in human neutrophils (35).…”

Section: Discussionmentioning

confidence: 95%

“…However, less is known about the role of a-adrenoceptors in the inflammatory response. The presence of a2-adrenergic receptors has been posited for both leukocytes and endothelial cells, based mainly on pharmacologic evidence (9)(10)(11)(12); in addition, significant experimental data support the view that these receptors act as inflammation modulators. The production of proinflammatory cytokines has been shown to be inhibited by the a2-agonist, in both an animal lung model (13) and a canine model of inflammation (14).…”

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confidence: 99%

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Prevention of Neutrophil Extravasation by α2-Adrenoceptor–Mediated Endothelial Stabilization

Herrera-García

Domínguez-Luis

Arce-Franco

et al. 2014

The Journal of Immunology

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Adrenergic receptors are expressed on the surface of inflammation-mediating cells, but their potential role in the regulation of the inflammatory response is still poorly understood. The objectives of this work were to study the effects of α2-adrenergic agonists on the inflammatory response in vivo and to determine their mechanism of action. In two mouse models of inflammation, zymosan air pouch and thioglycolate-induced peritonitis models, the i.m. treatment with xylazine or UK14304, two α2-adrenergic agonists, reduced neutrophil migration by 60%. The α2-adrenergic antagonist RX821002 abrogated this effect. In flow cytometry experiments, the basal surface expression of L-selectin and CD11b was modified neither in murine nor in human neutrophils upon α2-agonist treatment. Similar experiments in HUVEC showed that UK14304 prevented the activation-dependent upregulation of ICAM-1. In contrast, UK14304 augmented electrical resistance and reduced macromolecular transport through a confluent HUVEC monolayer. In flow chamber experiments, under postcapillary venule-like flow conditions, the pretreatment of HUVECs, but not neutrophils, with α2-agonists decreased transendothelial migration, without affecting neutrophil rolling. Interestingly, α2-agonists prevented the TNF-α–mediated decrease in expression of the adherens junctional molecules, VE-cadherin, β-catenin, and plakoglobin, and reduced the ICAM-1–mediated phosphorylation of VE-cadherin by immunofluorescence and confocal analysis and Western blot analysis, respectively. These findings indicate that α2-adrenoceptors trigger signals that protect the integrity of endothelial adherens junctions during the inflammatory response, thus pointing at the vascular endothelium as a therapeutic target for the management of inflammatory processes in humans.

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

Prevention of Neutrophil Extravasation by α2-Adrenoceptor–Mediated Endothelial Stabilization

Herrera-García

Domínguez-Luis

Arce-Franco

et al. 2014

The Journal of Immunology

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“…Zymosan causes hypersensitivity to mechanical stimulation of the hindpaw, which is dependent on expression of IL-1, IL-6, TNF␣, and reactive oxygen species and complement at the site of inflammation (Twining et al, 2004) and which is also dependent on activated microglia in the spinal cord (Milligan et al, 2003). Because lymphocytes (Titnchi and Clark, 1984) and macrophages (Spengler et al, 1990) express ␣2-adrenoceptors, we hypothesized that the phenotype of these leukocytes would be altered by clonidine and thereby repress hypersensitivity. To test this, we determined whether ␣2-adrenoceptor stimulation would reduce hyperalgesia in acute inflammatory neuritis and, if so, assessed the cell type(s) and cytokine gene expression changes by which these receptors act.…”

Section: Introductionmentioning

confidence: 99%

α2-Adrenoceptor Stimulation Transforms Immune Responses in Neuritis and Blocks Neuritis-Induced Pain

Romero‐Sandoval

McCall²,

Eisenach³

2005

J. Neurosci.

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Neuropathic pain may be primarily driven by immune responses in peripheral nerves. Peripherally released catecholamines may exacerbate neuropathic pain and also modulate immune responses in a complex and sometimes opposing manner by actions on multiple adrenoceptor subtypes. We showed previously that injection of the ␣2-adrenoceptor agonist clonidine at the site of peripheral nerve injury reduces pain behavior and local tissue pro-inflammatory cytokine content in rats. The current study used a model of acute inflammatory neuritis to test the efficacy and mechanisms of action of ␣2-adrenoceptor stimulation to reduce pain. Zymosan, injected on the sciatic nerve, caused hypersensitivity to mechanical stimuli ipsilateral to injection and contralaterally, so-called mirror image pain. Ipsilateral hypersensitivity was inhibited dose-dependently by perineural injection of clonidine. Zymosan increased leukocyte number at the site of injection 3 d later as well as their content of interleukin 1␣ (IL-1␣), IL-1␤, and IL-6. Perineural clonidine prevented both the increase in leukocyte number and cytokine expression induced by zymosan. Additionally, clonidine reduced the capacity of leukocytes to express pro-inflammatory cytokines as assessed by treatment of cells ex vivo with lipopolysaccharide, whereas no repression of IL-10 production occurred. Clonidine reduced the number of macrophages and lymphocytes as well as their expression of tumor necrosis factor ␣. All of the effects of clonidine were prevented by coadministration of an ␣2A-adrenoceptor-preferring antagonist. These results suggest that ␣2-adrenoceptor stimulation transforms cytokine gene expression, especially in macrophages and lymphocytes from a pro-to an anti-inflammatory profile in the setting of neuritis, likely relieving neuritis-induced pain by this mechanism.

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“…20 In addition, peripheral cells such as blood lymphocytes express D2, 21 D3, 22,23 D4, 23,24 D5 receptors, 25 M2, M3, M4, M5 receptors 26,27 and a1 28 and a2 receptors 29,30 using radioligand binding studies. Since pharmacological characterization remains difficult given the lack of suitable receptor-specific ligands, 31 the expression of neurotransmitter receptors by the detection of corresponding mRNAs has recently been undertaken.…”

Section: Introductionmentioning

confidence: 99%

Potential clozapine target sites on peripheral hematopoietic cells and stromal cells of the bone marrow

et al. 2003

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The antipsychotic drug clozapine, acts via interaction with selective neurotransmitter receptor systems. Its use however, is associated with lifethreatening agranulocytosis. The mechanism by which this occurs and its possible relationship with the drug's atypicality remain unclear. As a first step in identifying mechanistic pathways involved, profiling of neurotransmitter receptors on human neutrophils, mononuclear and bone marrow stromal cells as putative targets for clozapine-mediated toxicity was undertaken. Expression of mRNA encoding dopaminergic d2, d3, d4; serotonergic 5ht2a, 5ht2c, 5ht3, 5ht6, 5ht7; adrenergic a1a, a2; histaminergic h1 and muscarinic m1, m2, m3, m4, m5 receptors was analyzed by reverse transcription-polymerase chain reaction methods. While 5ht2c, 5ht6, m1 and m2 mRNA were undetected, the presence of the other receptors indicates sites at which clozapine could bind and induce toxicity of neutrophils and stromal components which regulate granulopoiesis. The functional significance of differential receptor expression while unknown, may argue for neural regulation of hematopoiesis.

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Alpha2-adrenoceptors in human lymphocytes: Direct characterisation by [3H]yohimbine binding

Cited by 47 publications

References 22 publications

Prevention of Neutrophil Extravasation by α2-Adrenoceptor–Mediated Endothelial Stabilization

Prevention of Neutrophil Extravasation by α2-Adrenoceptor–Mediated Endothelial Stabilization

α2-Adrenoceptor Stimulation Transforms Immune Responses in Neuritis and Blocks Neuritis-Induced Pain

Potential clozapine target sites on peripheral hematopoietic cells and stromal cells of the bone marrow

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