Chemical sympathectomy augments the severity of experimental allergic encephalomyelitis

神经肽Y及Th1/Th2细胞与多发性硬化Multiple sclerosis, neuropeptide Y ...

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Multiple sclerosis, neuropeptide Y and Th1/Th2 cell .... Chemical sympathectomy augments the severity of experimental allergic encephalomyelitis 《Journal ... scholar.ilib.cn/Abstract.aspx?A=xdkf200521094 - Similar pages - Note this

Maintenance of blood pressure is mostly dependent on sympathetic “tone”, and the sympathetic nerve innervates the entire vascular bed

Pharmacology and Physiology of Perivascular Nerves Regulating Vascular Function Role of Perivascular Sympathetic Nerves and Regional Differences in the Features of Sympathetic Innervation of the Vascular System

Hiromichi Tsuru1), Noriaki Tanimitsu2) and Tomohisa Hirai2)

1) Department of Pharmacology, Toho University School of Medicine 2) Department of Otorhinolaryngology, Hiroshima University School of Medicine

ABSTRACT: Maintenance of blood pressure is mostly dependent on sympathetic “tone”, and the sympathetic nerve innervates the entire vascular bed, excepting the capillaries. Although norepinephrine (NE) is the principal neurotransmitter released upon sympathetic nerve stimulation, neuropeptide Y and ATP are cotransmitters in various vascular tissues. In addition, dopamine and epinephrine, as well as acetylcholine, have been shown to be sympathetic neurotransmitters in specific vasculatures. Transmitter NE release is modified by a number of endogenous substances including the transmitter itself. Chronic denervation of the preganglionic fiber induces an increase in NE release per pulse, indicating postganglionic neuronal supersensitivity. So far, three main adrenoceptor types have been shown, α1, α2 and β, each of which is further divided into at least three subtypes, as well as the α1L-adrenoceptor, a phenotype of the cloned α1a-adrenoceptor, in the blood vessel. Thus, the response of vessels with different receptor types to a transmitter varies quantitatively and even qualitatively from one vessel to another. The remarkable diversity in the sympathetic innervation mechanism in the vascular system may play an important role in regional variations in the regulation of blood flow. The sympathetic nerve also exerts long-term trophic action on the blood vessel. In conclusion, the sympathetic nervous system plays an important role not only in the regulation of cardiovascular dynamics but in the maintenance of the vessel structure, as well.

The Japanese Journal of PharmacologyVol. 88 (2002) , No. 1 pp.9-13

The significant fall in left circumflex coronary flow was proportional to the decline in external heart work due to sympathectomy both at rest and und

E. Bassenge¹, J. Holtz¹, W. v. Restorff¹ and K. Oversohl¹

(1)	Physiologisches Institut der Ludwig-Maximilian-Universität München, Germany

Received: 18 April 1973

The exercise capacity and the increase of coronary and systemic hemodynamics under treadmill exercise were studied in 5 dogs, chemically sympathectomized with 6-hydroxy-dopamine.

Completeness of adrenergic denervation was verified by stimulation of the right stellate ganglion, by intravenous administration of tyramine, and by demonstration of supersensitivity to exogenous norepinephrine.

These dogs demonstrated a retarded adaptation of hemodynamics to a sudden start of exercise. A fall in mean arterial pressure below 45 mmHg within 10 to 15 sec lead to collapse. After a recovery period of 60–90 sec, moderate treadmill exercise could be continued; steady state attainment of hemodynamic parameters was considerably delayed.

A steady state of exercise with an O₂-consumption (vO₂) of 29.6±2.6 ml/min · kg and a cardiac outupt (CO) of 307±16 ml/min · kg was tolerated for at least 20 min.

An increase of vO₂ up to 42.0±1.7 ml/min · kg and of CO up to 357±13 ml/min · kg under exercise was tolerated for 5 min with steady state, maximal heart rate being 160±4 min^–1 at this level of exercise.

Mean arterial pressure and total peripheral resistance were significantly reduced at rest and during steady state of exercise as compared to controls prior to sympathectomy identical vO₂, whereas CO remained unchanged.

The significant fall in left circumflex coronary flow was proportional to the decline in external heart work due to sympathectomy both at rest and under exercise.

Differential Effects of Chemical Sympathectomy on Expression and Activity of Tyrosine Hydroxylase and Levels of Catecholamines and DOPA

Tyrosine hydroxylase (TH) mRNA and activity and concentrations of 3,4-dihydroxyphenylalanine (DOPA) and catecholamines were examined as markers of sympathetic innervation and catecholamine synthesis in peripheral tissues of sympathectomized and intact rats. Chemical sympathectomy with 6-hydroxydopamine (6-OHDA) markedly decreased norepinephrine and to a generally lesser extent TH activities and dopamine in most peripheral tissues (stomach, lung, testis, duodenum, pancreas, salivary gland, spleen, heart, kidney, thymus). Superior cervical ganglia, adrenals and descending aorta were unaffected and vas deferens showed a large 92% decrease in norepinephrine, but only a small 38% decrease in TH activity after 6-OHDA.

Minoru Kawamura^{1, 2}, Joan P. Schwartz¹, Takuo Nomura¹, Irwin J. Kopin¹, David S. Goldstein¹, Thanh-Truc Huynh¹, Douglas R. Hooper¹, Judith Harvey-White¹ and Graeme Eisenhofer¹

(1)	Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892

(2)	Institute of Bio-Active Science, Nippon Zoki Pharmaceutical Co., Ltd. Hyogo, 673-14, Japan

Volume 24, Number 1 / January, 1999
JournalNeurochemical Research

the sympathetic nervous system regulates the clinical and pathological manifestations of experimental autoimmune encephalomyelitis (EAE)

Neuropeptide Y (NPY) suppresses experimental autoimmune encephalomyelitis: NPY1 receptor-specific inhibition of autoreactive Th1 responses in vivo.

[My paper] Sammy Bedoui, Sachiko Miyake, Youwei Lin, Katsuichi Miyamoto, Shinji Oki, Noriyuki Kawamura, Annette Beck-Sickinger, Stephan von Hörsten, Takashi Yamamura

Department of Immunology, National Institute of Neuroscience, NCNP, Ogawahigashi, Kodaira, Tokyo, Japan.

Prior studies have revealed that the sympathetic nervous system regulates the clinical and pathological manifestations of experimental autoimmune encephalomyelitis (EAE), an autoimmune disease model mediated by Th1 T cells. Although the regulatory role of catecholamines has been indicated in the previous works, it remained possible that other sympathetic neurotransmitters like neuropeptide Y (NPY) may also be involved in the regulation of EAE. Here we examined the effect of NPY and NPY receptor subtype-specific compounds on EAE, actively induced with myelin oligodendrocyte glycoprotein 35-55 in C57BL/6 mice. Our results revealed that exogenous NPY as well as NPY Y(1) receptor agonists significantly inhibited the induction of EAE, whereas a Y(5) receptor agonist or a combined treatment of NPY with a Y(1) receptor antagonist did not inhibit signs of EAE. These results indicate that the suppression of EAE by NPY is mediated via Y(1) receptors. Furthermore, treatment with the Y(1) receptor antagonist induced a significantly earlier onset of EAE, indicating a protective role of endogenous NPY in the induction phase of EAE. We also revealed a significant inhibition of myelin oligodendrocyte glycoprotein 35-55-specific Th1 response as well as a Th2 bias of the autoimmune T cells in mice treated with the Y(1) receptor agonist. Ex vivo analysis further demonstrated that autoimmune T cells are directly affected by NPY via Y(1) receptors. Taken together, we conclude that NPY is a potent immunomodulator involved in the regulation of the Th1-mediated autoimmune disease EAE.

J. Immunol. 2003 Oct 1;171 (7):3451-8 14500640 (P,S,E,B) Cited:3

Autonomic innervation of immune organs and neuroimmune modulation.

Autonomic & Autacoid Pharmacology. 23(1):1-25, February 2003.
Mignini, F.; Streccioni, V.; Amenta, F.

Abstract:
Summary: 1 Increasing evidence indicates the occurrence of functional interconnections between immune and nervous systems, although data available on the mechanisms of this bi-directional cross-talking are frequently incomplete and not always focussed on their relevance for neuroimmune modulation.

2 Primary (bone marrow and thymus) and secondary (spleen and lymph nodes) lymphoid organs are supplied with an autonomic (mainly sympathetic) efferent innervation and with an afferent sensory innervation. Anatomical studies have revealed origin, pattern of distribution and targets of nerve fibre populations supplying lymphoid organs.

3 Classic (catecholamines and acetylcholine) and peptide transmitters of neural and non-neural origin are released in the lymphoid microenvironment and contribute to neuroimmune modulation. Neuropeptide Y, substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide represent the neuropeptides most involved in neuroimmune modulation.

4 Immune cells and immune organs express specific receptors for (neuro)transmitters. These receptors have been shown to respond in vivo and/or in vitro to the neural substances and their manipulation can alter immune responses. Changes in immune function can also influence the distribution of nerves and the expression of neural receptors in lymphoid organs.

5 Data on different populations of nerve fibres supplying immune organs and their role in providing a link between nervous and immune systems are reviewed. Anatomical connections between nervous and immune systems represent the structural support of the complex network of immune responses. A detailed knowledge of interactions between nervous and immune systems may represent an important basis for the development of strategies for treating pathologies in which altered neuroimmune cross-talking may be involved.

NPY in the regulation of autoimmune Th1 cells

Substantial evidence indicates a dysfunctional communication between the sympathetic nervous system and the immune system in Th1-mediated autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis. In this Opinion, we propose that the sympathetic regulation of immunity is not only mediated by catecholamines but also involves neuropeptide Y (NPY), an additional postganglionic SNS transmitter that is shown to modulate various immunological functions in vitro and in vivo. Based on recent experimental findings, we believe that a more precise understanding of the role of NPY in the regulation of autoimmune Th1 cells will provide novel insights into the neuroimmunological basis of autoimmunity.

Sammy Bedoui^a, Sachiko Miyake^c, Rainer H. Straub^b, Stephan von Hörsten^a and Takashi Yamamura^c,

^aDepartment of Functional and Applied Anatomy, Medical School of Hannover, 30625 Hannover, Germany

^bDepartment of Internal Medicine I, University Hospital Regensburg, 93042 Regensburg, Germany

^cDepartment of Immunology, National Institute of Neuroscience, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan

Available online 20 August 2004.

dual pro- and anti-inflammatory role of the sympathetic nervous system (SNS) in inflammatory joint disease - Sympathetic Neurotransmitters in Joint Inflammation

Rainer H. Straub MD^, and Peter Härle MD

Laboratory of Neuroendocrinoimmunology, Department of Internal Medicine I, University Hospital Regensburg, FJS-Allee 11, 93042 Regensburg, Germany

Available online 5 January 2005.

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This article demonstrates the dual pro- and anti-inflammatory role of the sympathetic nervous system (SNS) in inflammatory joint disease (IJD) by way of distinct adrenoceptors. The dual role of the SNS depends on involved compartments, timing of distinct effector mechanisms during the inflammatory process, availability of respective adrenoceptors on target cells, and an intricate shift from β-to- adrenergic signaling in the progressing course of the inflammatory disease (β-to- adrenergic shift). Additional critical points for the dual role of the SNS in inflammation are the underlying change of immune effector mechanisms during the process of disease progression and the behavior of sympathetic nerve fibers in inflamed tissue (nerve fiber loss). This is accompanied by a relative lack of anti-inflammatory glucocorticoids in relation to inflammation. In quintessence, in early stages of IJD, the SNS plays a predominantly proinflammatory role, whereas in late stages of the disease the SNS most probably exerts anti-inflammatory effects.