TY  - JOUR
  - Martin, F. C.,Anton, P. A.,Gornbein, J. A.,Shanahan, F.,Merrill, J. E.
  - 1993
  - January
  - Production of Interleukin-1 by Microglia in Response to Substance-P - Role for a Nonclassical Nk-1 Receptor
  - Validated
  - ()
  - 42
  - 11
  - 53
  - 6053
  - Substance P (SP) is a central and peripheral neurotransmitter which has been found in multiple sclerosis plaques. SP stimulates peripheral immune cells and may play a role in some chronic inflammatory diseases. Human peripheral monocyte/macrophages have been shown to produce the inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) in response to SP. Therefore, in this study we examined rat brain microglia for the presence of SP receptors and production of IL-1 and TNFalpha in response to SP. Microglia had 4900 +/- 950 (mean +/- SE) receptors per cell fitting a two-site model. Four percent of these were high-affinity receptors with a K(d) of 8.2 x 10(-8) M +/- 3.6 x 10(-8) M (mean +/- SE), and 96% of them were low-affinity receptors with a K(d) of 2.1 X 10(-6) M +/- 5.2 x 10(-7)M (mean +/- SE). Competitive studies with CP 96,345 and other SP analogs demonstrate these to be non-classical NK-1 receptors. SP alone did not stimulate IL-1 or TNFalpha production. However, SP in synergy with lipopolysaccharide (LPS) quadrupled IL-1 production compared to LPS alone, but did not affect TNFalpha production. These results have implications for certain inflammatory conditions in the central nervous system.Substance P (SP) is a central and peripheral neurotransmitter which has been found in multiple sclerosis plaques. SP stimulates peripheral immune cells and may play a role in some chronic inflammatory diseases. Human peripheral monocyte/macrophages have been shown to produce the inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) in response to SP. Therefore, in this study we examined rat brain microglia for the presence of SP receptors and production of IL-1 and TNFalpha in response to SP. Microglia had 4900 +/- 950 (mean +/- SE) receptors per cell fitting a two-site model. Four percent of these were high-affinity receptors with a K(d) of 8.2 x 10(-8) M +/- 3.6 x 10(-8) M (mean +/- SE), and 96% of them were low-affinity receptors with a K(d) of 2.1 X 10(-6) M +/- 5.2 x 10(-7)M (mean +/- SE). Competitive studies with CP 96,345 and other SP analogs demonstrate these to be non-classical NK-1 receptors. SP alone did not stimulate IL-1 or TNFalpha production. However, SP in synergy with lipopolysaccharide (LPS) quadrupled IL-1 production compared to LPS alone, but did not affect TNFalpha production. These results have implications for certain inflammatory conditions in the central nervous system.
  - 0165-57280165-5728
  - ://WOS:A1993KJ76600007://WOS:A1993KJ76600007
DA  - 1993/01
ER  - 

@article{V235380050,
   = {Martin,  F. C. and Anton,  P. A. and Gornbein,  J. A. and Shanahan,  F. and Merrill,  J. E. },
   = {1993},
   = {January},
   = {Production of Interleukin-1 by Microglia in Response to Substance-P - Role for a Nonclassical Nk-1 Receptor},
   = {Validated},
   = {()},
   = {42},
   = {11},
  pages = {53--6053},
   = {{Substance P (SP) is a central and peripheral neurotransmitter which has been found in multiple sclerosis plaques. SP stimulates peripheral immune cells and may play a role in some chronic inflammatory diseases. Human peripheral monocyte/macrophages have been shown to produce the inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) in response to SP. Therefore, in this study we examined rat brain microglia for the presence of SP receptors and production of IL-1 and TNFalpha in response to SP. Microglia had 4900 +/- 950 (mean +/- SE) receptors per cell fitting a two-site model. Four percent of these were high-affinity receptors with a K(d) of 8.2 x 10(-8) M +/- 3.6 x 10(-8) M (mean +/- SE), and 96% of them were low-affinity receptors with a K(d) of 2.1 X 10(-6) M +/- 5.2 x 10(-7)M (mean +/- SE). Competitive studies with CP 96,345 and other SP analogs demonstrate these to be non-classical NK-1 receptors. SP alone did not stimulate IL-1 or TNFalpha production. However, SP in synergy with lipopolysaccharide (LPS) quadrupled IL-1 production compared to LPS alone, but did not affect TNFalpha production. These results have implications for certain inflammatory conditions in the central nervous system.Substance P (SP) is a central and peripheral neurotransmitter which has been found in multiple sclerosis plaques. SP stimulates peripheral immune cells and may play a role in some chronic inflammatory diseases. Human peripheral monocyte/macrophages have been shown to produce the inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) in response to SP. Therefore, in this study we examined rat brain microglia for the presence of SP receptors and production of IL-1 and TNFalpha in response to SP. Microglia had 4900 +/- 950 (mean +/- SE) receptors per cell fitting a two-site model. Four percent of these were high-affinity receptors with a K(d) of 8.2 x 10(-8) M +/- 3.6 x 10(-8) M (mean +/- SE), and 96% of them were low-affinity receptors with a K(d) of 2.1 X 10(-6) M +/- 5.2 x 10(-7)M (mean +/- SE). Competitive studies with CP 96,345 and other SP analogs demonstrate these to be non-classical NK-1 receptors. SP alone did not stimulate IL-1 or TNFalpha production. However, SP in synergy with lipopolysaccharide (LPS) quadrupled IL-1 production compared to LPS alone, but did not affect TNFalpha production. These results have implications for certain inflammatory conditions in the central nervous system.}},
  issn = {0165-57280165-5728},
   = {://WOS:A1993KJ76600007://WOS:A1993KJ76600007},
  source = {IRIS}
}