dopamine receptors are widely expressed because they are involved in the control of locomotion, cognition, emotion

The D2 and D3 receptors vary in certain tissues and species as a result of alternative splicing, and the human D4 receptor gene exhibits extensive polymorphic variation. In the central nervous system, dopamine receptors are widely expressed because they are involved in the control of locomotion, cognition, emotion, and affect as well as neuroendocrine secretion. In the periphery, dopamine receptors are present more prominently in kidney, vasculature, and pituitary, where they affect mainly sodium homeostasis, vascular tone, and hormone secretion. Numerous genetic linkage analysis studies have failed so far to reveal unequivocal evidence for the involvement of one of these receptors in the etiology of various central nervous system disorders. However, targeted deletion of several of these dopamine receptor genes in mice should provide valuable information about their physiological functions.



PHYSIOLOGICAL REVIEWS Vol. 78 No. 1 January 1998, pp. 189-225
Copyright ©1998 The American Physiological Society
Dopamine Receptors: From Structure to Function

CRISTINA MISSALE, S. RUSSEL NASH, SUSAN W. ROBINSON, MOHAMED JABER, AND MARC G. CARON

Departments of Cell Biology and Medicine, Howard Hughes Medical Institute Laboratories, Duke University Medical Center, Durham, North Carolina

Changes in dopamine D2 receptors and 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine uptake in the brain of 6-hydroxydopamine-lesioned rats

Ishida Y, Kawai K, Magata Y, Takeda R, Hashiguchi H, Abe H, Mukai T, Saji H.

Department of Psychiatry, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan.

We studied tracer distributions in positron emission tomography of ligands for dopamine D1 receptors ([11C]SCH23390) and D2 receptors ([11C]raclopride) and the dopamine precursor analog 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA), as a measurement of presynaptic dopaminergic function, in the brain after 6-hydroxydopamine lesioning of the medial forebrain bundle in rats. The unilateral lesions were confirmed behaviorally by methamphetamine-induced rotation 2 weeks after lesioning, and the brains were analyzed by tissue dissection following an intravenous bolus of each tracer 3 weeks after lesioning. [11C]Raclopride, but not [11C]SCH23390, showed a higher accumulation in the striatum on the lesion side compared with that on the non-lesioned (intact) side. On the other hand, a lower accumulation of [18F]FDOPA was found in the striatum and cerebral cortex on the lesion side. Our studies demonstrate upregulation of dopamine D2 receptors in the striatum and a decrease in FDOPA uptake in both the striatum and cerebral cortex ipsilateral to the 6-hydroxydopamine lesions. Therefore, the combination of a D2 antagonist and FDOPA may provide a potentially useful method for assessing the effects of dopamine depletion in Parkinson's disease. Copyright 2004 S. Karger AG, Basel.

Neurodegener Dis. 2004;1(2-3):109-12.

S - increase in activity of the adrenal gland.

Depletion and recovery of catecholamines in several organs of rats treated with reserpine.

[My paper] Rubén Martínez-Olivares, Iván Villanueva, Radu Racotta, Manuel Piñón
Depto. de Fisiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala s/n. Col. Santo Tomás, DF. CP. 11340, México.

Chemical sympathectomy with reserpine depletes catecholamines in every neuronal or nonneuronal cell producing a nonspecific temporal sympathectomy. After reserpine administration, most of the drug is distributed to tissues based on their blood flow and would then either be metabolized or be reversibly bound in lipid depots from where it might be released. Consequently, reserpine concentration and the catecholamine-depleting effect in the various tissues are expected to differ according to the route of administration. This study was designed to compare the effects of intraperitoneal (i.p.) and subcutaneous (s.c.) administration of reserpine on catecholamine depletion and recovery in the liver, portal vein, and adrenal gland on days 1, 4, and 10 after reserpine dosage. Catecholamine determinations were extended to 25 days after the treatment only in s.c. reserpine-treated rats and adding samples of heart and brown adipose tissue to the testing. I.p. and s.c. reserpine administration had the same norepinephrine-depleting effect in the portal vein and liver but full recovery was present in both tissues only in i.p. reserpine-treated rats. In the adrenal gland, both routes of administration produced the same depleting and recovery effect of norepinephrine and epinephrine concentrations. A significant temporary overshoot in epinephrine levels was observed several days after s.c. reserpine treatment. Except for the liver, reserpine injected s.c. depleted norepinephrine concentrations significantly in all other tissues up to the end of the experiment. Our results suggest that chemical sympathectomy caused by reserpine administered s.c. produces a generalized and prolonged decrease in peripheral sympathetic activity that could be compensated by an increase in activity of the adrenal gland.

Auton Neurosci. 2006 May 22; : 16723281 (P,S,E,B)

partial denervation by lesion of peripheral nerve or by tissue destruction induces a change in peripheral nociceptors, making them excitable

Edward R. Perl*

Department of Cell and Molecular Physiology, CB 7545, University of North Carolina, Chapel Hill, NC 27599

Control of expression of molecular receptors for chemical messengers and modulation of these receptors' activity are now established as ways to alter cellular reaction. This paper extends these mechanisms to the arena of pathological pain by presenting the hypothesis that increased expression of alpha -adrenergic receptors in primary afferent neurons is part of the etiology of pain in classical causalgia. It is argued that partial denervation by lesion of peripheral nerve or by tissue destruction induces a change in peripheral nociceptors, making them excitable by sympathetic activity and adrenergic substances. This excitation is mediated by alpha -adrenergic receptors and has a time course reminiscent of experimental denervation supersensitivity. The change in neuronal phenotype is demonstrable after lesions of mixed nerves or of the sympathetic postganglionic supply. Similar partial denervations also produce a substantial increase in the number of dorsal root ganglion neurons evidencing the presence of alpha -adrenergic receptors. The hypothesis proposes the increased presence of alpha -adrenergic receptors in primary afferent neurons to result from an altered gene expression triggered by cytokines/growth factors produced by disconnection of peripheral nerve fibers from their cell bodies. These additional adrenergic receptors are suggested to make nociceptors and other primary afferent neurons excitable by local or circulating norepinephrine and epinephrine. For central pathways, the adrenergic excitation would be equivalent to that produced by noxious events and would consequently evoke pain. In support, evidence is cited for a form of denervation supersensitivity in causalgia and for increased expression of human alpha -adrenergic receptors after loss of sympathetic activity.

Vol. 96, Issue 14, 7664-7667, July 6, 1999


PNAS

Bendroflumethiazide; Nadolol Tablets

What should my health care professional know before I receive Bendroflumethiazide; Nadolol?

They need to know if you have any of these conditions:

*

asthma, bronchitis or bronchospasm
*

autoimmune disease such as lupus
*

chest pain (angina)
*

circulation problems, or blood vessel disease (such as Raynaud's disease)
*

depression
*

diabetes
*

electrolyte imbalance (such as low or high levels of potassium in the blood)
*

emphysema, COPD, or other lung disease
*

gout
*

heart disease (such as heart failure or a history of heart attack)
*

kidney disease
*

liver disease
*

muscle weakness or myasthenia gravis
*

pancreatitis
*

pheochromocytoma
*

post-sympathectomy
*

psoriasis
*

thyroid disease
*

unusually slow heartbeat

Supersensitivity of effector cells (smooth muscle) occurs following long-term use, reminiscent of surgical sympathectomy.

Guanethidine and guanadrel

Adverse effects and toxicity: Postural hypotension and decreased blood flow to heart and brain. It causes delayed ejaculaiton in men, increased GI motility and diarrhea. Supersensitivity of effector cells (smooth muscle) occurs following long-term use, reminiscent of surgical sympathectomy.

The antihypertensive effects of thiazides may be enhanced in the post-sympathectomy patient.

PRODUCT MONOGRAPH

TENORETIC

Antihypertensive Agent

PRECAUTIONS:

The antihypertensive effects of thiazides may be enhanced in the post-sympathectomy patient.

Posterior Left Thoracic Cardiac Sympathectomy by Surgical Division of the Sympathetic Chain: An Alternative Approach to Treatment of the Long QT Syndr

Although high thoracic left Sympathectomy via art anterior surgical approach is a highly efficacious treatment for refractory ventricular arrhythmias in patients with the long QT syndrome, the degree of sympathetic denervation has been variable, success of the operation is influenced by anatomical differences between patients, and Horner's syndrome may result. We hypothesized that interruption of sympathetic input to the heart could be accomplished using a posterior thoracic approach to this variable and often complex anatomy by division of the sympathetic chain rather than by direct destruction of the stellate and superior thoracic ganglia with the more conventional anterior, supraclavicular approach. In addition, the posterior approach should decrease the risk of Horner's syndrome by avoiding the ocular sympathetic efferent nerves. This posterior approach is described in five patients with the long QT syndrome and recurrent ventricular arrhythmias. After a mean follow-up of 18 ± 12 months, all are alive without Homer's syndrome.

* ANDREW E. EPSTEIN11Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama,
* MICHAEL J. ROSNER,**Division of Neurosurgery, Department of Surgery, The University of Alabama at Birmingham, Birmingham, Alabama
* GILBERT R. HAGEMAN,****Department of Physiology and Biophysics, The University of Alabama at Birmingham, Birmingham, Alabama
* JAMES H. BAKER, II11Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama,
* VANCE J. PLUMB11Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, and
* G. NEAL KAY11Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama

*
1Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama *Division of Neurosurgery, Department of Surgery, The University of Alabama at Birmingham, Birmingham, Alabama **Department of Physiology and Biophysics, The University of Alabama at Birmingham, Birmingham, Alabama

Pindolol - inhibition of ejaculaiton

AccessPharmacy.com
... similar to those of surgical sympathectomy, including inhibition of ejaculation, ..... Daily doses of pindolol start at 10 mg; of acebutolol, at 400 mg; ...
www.accesspharmacy.com/Content.aspx?searchStr=acebutolol&aid=2500340 - 139k - Cached - Similar pages

Potentiation of the antihypertensive effect occurs with ganglionic or peripheral adrenergic blocking drugs and in the post sympathectomy patient

Name of the medicine: BARBLOC
The active ingredient of Barbloc is pindolol.

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

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.

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.

This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier.

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.