ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: The CNS modulates immune cells by direct synaptic-likecontacts in the brain and at peripheral sites, such as lymphoid organs. Tostudy the nerve-macrophage communication, a superfusion method was used toinvestigate cotransmission of neuropeptide Y (NPY) with norepinephrine (NE),with interleukin (IL)-6 secretion used as the macrophage read-out parameter.Spleen tissue slices spontaneously released NE, NPY, and IL-6 leading to asuperfusate concentration at 3-4 h of 1 nM, 10 pM, and 120pg/ml, respectively. Under these conditions, NPY dose-dependently inhibitedIL-6 secretion with a maximum effect at 10-10M(p = 0.012) and 10-9M (p 〈 0.001).Simultaneous addition of NPY at 10-9M and theα-2-adrenergic agonist p-aminoclonidine further inhibited IL-6secretion (p 〈 0.05). However, simultaneous administration of NPYat 10-9M and the β-adrenergic agonist isoproterenolat 10-6M or NE at 10-6Msignificantly increased IL-6 secretion (p 〈 0.005). To objectifythese differential effects of NPY, electrical field stimulation of spleenslices was applied to release endogenous NPY and NE. Electrical fieldstimulation markedly reduced IL-6 secretion, which was attenuated by the NPYY1 receptor antagonist BIBP 3226 (10-7M, p = 0.039;10-8M, p = 0.035). This indicates that NPY increases theinhibitory effect of endogenous NE, which is mediated at low NE concentrationsvia α-adrenoceptors. Blockade of α-adrenoceptors attenuatedelectrically induced inhibition of IL-6 secretion (p 〈 0.001),which was dose-dependently abrogated by BIBP 3226. This indicates that underblockade of α-adrenoceptors endogenous NPY supports the stimulatingeffect of endogenous NE via β-adrenoceptors. These experimentsdemonstrate the ambiguity of NPY, which functions as a cotransmitter of NE inthe nerve-macrophage interplay.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.2000.0752464.x
Permalink
