title: Effects of MK-801 and amphetamine treatments on allergic lung inflammatory response in mice.
abstract: 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.
authors: Neuroimmunomodulation Research Group, Department of Pathology, School of Veterinary Medicine, University of São Paulo, São Paulo, SP, Brazil.
authors: Eduardo Kenji
authors: EK
authors: Hamasato
authors: Ana Paula
authors: AP
authors: Ligeiro de Oliveira
authors: Adriana
authors: A
authors: Lino-dos-Santos-Franco
authors: Alison
authors: A
authors: Ribeiro
authors: Viviane
authors: V
authors: Ferraz de Paula
authors: Jean Pierre Schatzmann
authors: JP
authors: Peron
authors: Amílcar Sabino
authors: AS
authors: Damazo
authors: Wothan
authors: W
authors: Tavares-de-Lima
authors: João
authors: J
authors: Palermo-Neto
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003345:Corticosterone / Q000097:blood / Q000276:immunology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D007378:Interleukins / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D007378:Interleukins; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D010047:Ovalbumin; D000661:Amphetamine; D003345:Corticosterone