Neuropeptide Y cotransmission with norepinephrine in the sympathetic nerve-macrophage interplay

Straub, Rainer H. and Schaller, Thomas and Miller, Luitpold E. and von Hoersten, Stephan and Jessop, David S. and Falk, Werner and Schoelmerich, Juergen (2000) Neuropeptide Y cotransmission with norepinephrine in the sympathetic nerve-macrophage interplay. JOURNAL OF NEUROCHEMISTRY, 75 (6). pp. 2464-2471. ISSN 0022-3042

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Abstract

The CNS modulates immune cells by direct synaptic-like contacts in the brain and at peripheral sites, such as lymphoid organs. To study the nerve-macrophage communication, a superfusion method was used to investigate 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 a superfusate concentration at 3-4 h of 1 nM, 10 pM, and 120 pg/ml, respectively. Under these conditions, NPY dose-dependently inhibited IL-6 secretion with a maximum effect at 10(-10) M (p = 0.012) and 10(-9) M (p < 0.001). Simultaneous addition of NPY at 10(-9) M and the <alpha>2-adrenergic agonist p-aminoclonidine further inhibited IL-6 secretion (p < 0.05). However, simultaneous administration of NPY at 10(-9) M and the <beta>-adrenergic agonist isoproterenol at 10(-6) M Or NE at 10(-6) M significantly increased IL-6 secretion (p < 0.005). To objectify these differential effects of NPY, electrical field stimulation of spleen slices was applied to release endogenous NPY and NE. Electrical field stimulation markedly reduced IL-6 secretion, which was attenuated by the NPY Y1 receptor antagonist BIBP 3226 (10(-7) M, p = 0.039; 10(-8) M, p = 0.035). This indicates that NPY increases the inhibitory effect of endogenous NE, which is mediated at low NE concentrations via <alpha>-adrenoceptors. Blockade of alpha -adrenoceptors attenuated electrically induced inhibition of IL-6 secretion (p < 0.001), which was dose-dependently abrogated by BIBP 3226. This indicates that under blockade of <alpha>-adrenoceptors endogenous NPY supports the stimulating effect of endogenous NE via beta -adrenoceptors. These experiments demonstrate the ambiguity of NPY, which functions as a cotransmitter of NE in the nerve-macrophage interplay.

Item Type: Article
Uncontrolled Keywords: CYCLIC-AMP ACCUMULATION; SMOOTH-MUSCLE CELLS; RAT VAS-DEFERENS; PANCREATIC-POLYPEPTIDE; MURINE SPLEEN; ADENOSINE 5'-TRIPHOSPHATE; INTERLEUKIN-6 SECRETION; PEPTIDE-YY; NORADRENALINE; LOCALIZATION; neuropeptide Y; norepinephrine; neuroimmune interaction; spleen; macrophage; cytokines
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 15 Mar 2022 06:08
Last Modified: 15 Mar 2022 06:08
URI: https://pred.uni-regensburg.de/id/eprint/42016

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