Effects of MK-801 and amphetamine treatments on allergic lung inflammatory response in mice
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
16/04/2014
16/04/2014
16/08/2013
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Resumo |
Glutamate acts as a neurotransmitter within the Central Nervous System (CNS) and modifies immune cell activity. In lymphocytes, NMDA glutamate receptors regulate intracellular calcium, the production of reactive oxygen species and cytokine synthesis. MK-801, a NMDA receptor open-channel blocker, inhibits calcium entry into mast cells, thereby preventing mast cell degranulation. Several lines of evidence have shown the involvement of NMDA glutamate receptors in amphetamine (AMPH)-induced effects. AMPH treatment has been reported to modify allergic lung inflammation. This study evaluated the effects of MK-801 (0.25mg/kg) and AMPH (2.0mg/kg), given alone or in combination, on allergic lung inflammation in mice and the possible involvement of NMDA receptors in this process. In OVA-sensitized and challenged mice, AMPH and MK-801 given alone decreased cellular migration into the lung, reduced IL-13 and IL10 levels in BAL supernatant, reduced ICAM-1 and L-selectin expression in granulocytes in the BAL and decreased mast cell degranulation. AMPH treatment also decreased IL-5 levels. When both drugs were administered, treatment with MK-801 reversed the decrease in the number of eosinophils and neutrophils induced by AMPH in the BAL of OVA-sensitized and challenged mice as well as the effects on the expression of L-selectin and ICAM-1 in granulocytes, the IL-10, IL-5 and IL-13 levels in BAL supernatants and increased mast cell degranulation. At the same time, treatment with MK-801, AMPH or with MK-801+AMPH increased corticosterone serum levels in allergic mice. These results are discussed in light of possible indirect effects of AMPH and MK-801 via endocrine outflow from the CNS (i.e., HPA-axis activity) to the periphery and/or as a consequence of the direct action of these drugs on immune cell activity, with emphasis given to mast cell participation in the allergic lung response of mice. FAPESP, 2009/51886-3 FAPESP, 2009/01826-4 CNPq, 578014/2008-4 CNPq, 300764/2010-3 |
Identificador |
International Immunopharmacology, Amsterdam, v.16, n.4, p.436-443, 2013 http://www.producao.usp.br/handle/BDPI/44547 10.1016/j.intimp.2013.04.019 |
Idioma(s) |
eng |
Publicador |
Elsevier Science Amsterdam |
Relação |
International Immunopharmacology |
Direitos |
restrictedAccess Elsevier B.V. |
Palavras-Chave | #Amphetamine #MK-801 #Adhesion molecules #Cytokines #Allergic lung inflammation #HPA-axis #CITOCINAS #INFLAMAÇÃO #PULMÃO #ALERGIA #SISTEMA NERVOSO CENTRAL #MOLÉCULAS DE ADESÃO CELULAR |
Tipo |
article original article publishedVersion |