Induction of muscarinic receptor subtypes in monocytic/macrophagic cells differentiated from EoL-1 cells

Mita, Yoshinori; Dobashi, Kunio; Suzuki, Kouki; Mori, Masataka; Nakazawa, Takahiro

doi:10.1016/0014-2999(95)00722-9

Cited by 26 publications

(12 citation statements)

References 19 publications

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“…Muscarinic receptors are expressed on immune cells, including macrophages (15,31,32), which produce TNF during endotoxemia (33,34). Vagal efferents, distributed throughout the reticuloendothelial system and other peripheral organs are positioned to rapidly transmit the antiinflammatory signal to these cells.…”

Section: Discussionmentioning

confidence: 99%

“…Peripheral muscarinic receptors have an important mediating role in the vagus-nerve control of vital physiological functions. The presence of muscarinic receptors has been also reported on peripheral immune TNF-producing cells, including macrophages, monocytes, lymphocytes, and mast cells (15)(16)(17). To determine whether TNF release can be modulated by peripheral muscarinic receptor activation in vivo, we injected sublethal doses of muscarine i.v.…”

Section: Peripheral Muscarinic Receptors Are Not Essential For the Rementioning

confidence: 99%

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Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia

Pavlov

Ochani

Gallowitsch-Puerta

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

300

215

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TNF has a critical mediator role in inflammation and is an important therapeutic target. We recently discovered that TNF production is regulated by neural signals through the vagus nerve. Activation of this ''cholinergic antiinflammatory pathway'' inhibits the production of TNF and other cytokines and protects animals from the inflammatory damage caused by endotoxemia and severe sepsis. Here, we describe a role for central muscarinic acetylcholine receptors in the activation of the cholinergic antiinflammatory pathway. Central muscarinic cholinergic activation by muscarine, the M1 receptor agonist McN-A-343, and the M2 receptor antagonist methoctramine inhibited serum TNF levels significantly during endotoxemia. Centrally administered methoctramine stimulated vagus-nerve activity measured by changes in instantaneous heart-rate variability. Blockade of peripheral muscarinic receptors did not abolish antiinflammatory signaling through the vagus nerve, indicating that peripheral muscarinic receptors on immune cells are not required for the cytokine-regulating activities of the cholinergic antiinflammatory pathway. The role of central muscarinic receptors in activating the cholinergic antiinflammatory pathway is of interest for the use of centrally acting muscarinic cholinergic enhancers as antiinflammatory agents. muscarinic receptors ͉ systemic inflammation ͉ TNF ͉ vagus nerve T he overproduction of cytokines, including TNF, mediates tissue damage during the response to injury or pathogenic invasion (1). Physiological and molecular mechanisms that control TNF production maintain cytokine homeostasis and minimize or prevent damage during the host response to infection, injury, arthritis, and other disorders (1-3). Recently, we found (4-6) that electrical or pharmacological activation of the efferent vagus nerve inhibits the release of TNF and attenuates the development of endotoxin-induced shock in rodents. Stimulation of the efferent vagus nerve activates the release of acetylcholine. Although the vagus nerve is a ''classical'' cholinergic regulator of visceral functions in which peripheral muscarinic acetylcholine receptors have a major mediating role, the vagusnerve cytokine-inhibiting activity (which is termed ''the cholinergic antiinflammatory pathway'') requires signaling through nicotinic ␣ 7 subunit-containing receptors (4, 5).Studies have implicated muscarinic receptor-dependent mechanisms in the central modulation and integration of vagal regulation of visceral functions. For example, vagus nerve control of glycogen synthesis in the liver, the Bezold-Jarish cardiovascular reflex and the regulation of exocrine pancreatic secretion are modulated centrally by brain muscarinic receptor mechanisms (7-10). Thus, we reasoned that brain muscarinic receptors could be involved in the central regulation of the vagus-nerve immunomodulatory function. Our results indicate that central cholinergic activation by selective muscarinic receptor ligands significantly inhibits systemic TNF in endotoxemic rats and activates th...

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Section: Discussionmentioning

confidence: 99%

Section: Peripheral Muscarinic Receptors Are Not Essential For the Rementioning

confidence: 99%

Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia

Pavlov

Ochani

Gallowitsch-Puerta

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

300

215

View full text Add to dashboard Cite

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“…This, in turn, would alleviate the control over macrophage production of proinflammatory cytokines, increasing the circulation concentration of such cytokines and inducing further proliferative and cell activation signals (13,14,32,48). Myeloid cells also carry nicotinic (14) and muscarinic (35,49) ACh receptors. However, others have reported no direct ACh effects on peripheral blood cells (13), suggesting that the cholinergic effects on them operate indirectly through cytokine production.…”

Section: Catalytic and Nonenzymatic Properties Of Ache-r Are Most Likmentioning

confidence: 99%

Hydrolytic and Nonenzymatic Functions of Acetylcholinesterase Comodulate Hemopoietic Stress Responses

Grisaru¹,

Pick

Perry

et al. 2006

The Journal of Immunology

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Glucocorticoid-initiated granulocytosis, excessive proliferation of granulocytes, persists after cortisol levels are lowered, suggesting the involvement of additional stress mediator(s). In this study, we report that the stress-induced acetylcholinesterase variant, AChE-R, and its cleavable, cell-penetrating C-terminal peptide, ARP, facilitate granulocytosis. In postdelivery patients, AChE-R-expressing granulocyte counts increased concomitantly with serum cortisol and AChE activity levels, yet persisted after cortisol had declined. Ex vivo, mononuclear cells of adult peripheral blood responded to synthetic ARP26 by overproduction of hemopoietically active proinflammatory cytokines (e.g., IL-6, IL-10, and TNF-α). Physiologically relevant ARP26 levels promoted AChE gene expression and induced the expansion of cultured CD34+ progenitors and granulocyte maturation more effectively than cortisol, suggesting autoregulatory prolongation of ARP effects. In vivo, transgenic mice overexpressing human AChE-R, unlike matched controls, showed enhanced expression of the myelopoietic transcription factor PU.1 and maintained a stable granulocytic state following bacterial LPS exposure. AChE-R accumulation and the consequent inflammatory consequences can thus modulate immune responses to stress stimuli.

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“…A linhagem de células da leucemia eosinofílica (EoL-1) é outro sistema celular que pode ser utilizado para o estudo dos receptores M5 endógenos. Nessas células, a expressão de RNAm para receptores M5 e M3 é aumentada na presença de interferon, o que é necessário para a diferenciação das células EoL-1 em macrófagos maturos 29 .…”

Section: Figuraunclassified

Sistema colinérgico: revisitando receptores, regulação e a relação com a doença de Alzheimer, esquizofrenia, epilepsia e tabagismo

Ventura¹,

Abreu²,

Freitas³

et al. 2010

Rev. psiquiatr. clín.

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Sistema colinérgico: revisitando receptores, regulação e a relação com a doença de Alzheimer, esquizofrenia, epilepsia e tabagismo Resumo Objetivo: Revisar a estrutura e o funcionamento do sistema colinérgico central ressaltando seu papel na fisiologia e na fisiopatologia das doenças de Alzheimer e Parkinson, esquizofrenia, epilepsia e tabagismo. Método: Foi realizada uma pesquisa bibliográfica no MedLine, LILACS, PubMed e ISI, e na Biblioteca da Fundação Oswaldo Cruz, RJ, selecionando-se o período de 1914 a 2009, utilizando os descritores: "receptors", "cholinergic", "Alzheimer disease", "schizophrenia", "epilepsy" e "smoking", além de referências cruzadas dos artigos selecionados e análise adicional de referências na literatura específica do tema. Resultados: Efeitos importantes da ativação de receptores colinérgicos nicotínicos e muscarínicos sobre o desenvolvimento do sistema nervoso central (SNC) têm sido descritos. A dessensibilização e a internalização dos receptores acoplados à proteína G mediadas pela ativação de proteínas cinases têm sido descritas em proliferação, diferenciação e morte celular, além de síndromes neuropsiquiátricas. Conclusão: As informações produzidas a partir de estudos do sistema de neurotransmissão colinérgica podem auxiliar no desenvolvimento de medicamentos mais específicos para o tratamento da doença de Alzheimer, esquizofrenia, epilepsia e tabagismo.Ventura ALM, et al. / Rev Psiq Clín. 2010;37(2):66-72 Palavras-chave: Receptores colinérgicos, doença de Alzheimer, esquizofrenia, epilepsia, tabagismo. AbstractObjective: To review articles regarding important topics about cholinergic system and its ionotropic and G-protein coupled receptors as well as their regulation, also enlightening its importance in central nervous system (CNS) development and in several neuropsychiatric conditions such as Alzheimer disease, schizophrenia, epilepsy and smoking. Method: Bibliographical research was completed through MedLine, LILACS, PubMed, ISI and the Fundação Oswaldo Cruz Library, RJ, specifically for 1914 to 2009, using the descritors: "receptors", "cholinergic", Alzheimer "disease", "schizophrenia", "epilepsy" and "smoking", in addition to the cross-reference of the articles selected and further analyses of bibliographical references on the theme. Results: Currently literature describes important effects of nicotinic and muscarinic receptors activation on development of central nervous system (CNS). The protein G coupled receptors dessensibilization and internalization mediated by kinases have been described in proliferation, differentiation and cell death, and also in neurologic disorders. Discussion: The importance of the cholinergic system and its relationship with pathologies such as Alzheimer disease, schizophrenia, epilepsy is evident. The data produced so far may help on planning medicaments more specific for these pathologies treatment.Ventura ALM, et al. / Rev Psiq Clín. 2010;37(2):66-72 Keywords: Receptors, cholinergic, Alzheimer disease, schizophrenia, epilepsy, smoking. ...

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Induction of muscarinic receptor subtypes in monocytic/macrophagic cells differentiated from EoL-1 cells

Cited by 26 publications

References 19 publications

Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia

Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia

Hydrolytic and Nonenzymatic Functions of Acetylcholinesterase Comodulate Hemopoietic Stress Responses

Sistema colinérgico: revisitando receptores, regulação e a relação com a doença de Alzheimer, esquizofrenia, epilepsia e tabagismo

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