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      Plasma Aminopeptidase Activities in Rats after Left and Right Intrastriatal Administration of 6-Hydroxydopamine

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          Abstract

          Asymmetries in the neuroendocrine system extend from central structures to paired endocrine glands and their innervation. In addition to the well-known asymmetry in the function of brain dopamine, there are also asymmetries in the peripheral response to experimental hemi-parkinsonism, performed by means of lesions of the nigrostriatal system with 6-hydroxydopamine (6-OHDA) injections into the left or right hemisphere. Therefore, it is speculated that the neuroendocrine system would also be asymmetrically affected in experimental hemi-parkinsonism. Aminopeptidases (AP) play a major role in the control of peptide concentration at both central and peripheral levels in tissues and blood, thus reflecting the functional status of their endogenous substrates. Therefore, to evaluate the peripheral response of hemi-parkinsonism, we have performed a comprehensive study of plasma AP activities after lesions of the nigrostriatal system with 6-OHDA administered into either left or right striatum of adult male rats. Saline was injected into control groups. AlaAP, CysAP, AspAP and GluAP activities were determined in plasma, using specific arylamides as substrates. Plasma AlaAP activity increased 3-fold (p < 0.001) whereas AspAP activity decreased by 30% (p < 0.05) after lesion of the right hemisphere. In contrast, CysAP and GluAP activities increased significantly after lesion of the left hemisphere by 200 and 50%, respectively (p < 0.05). The main discovery of the present results demonstrates that experimental hemi-parkinsonism affects differentially the plasma AP activities depending on the hemisphere in which the lesion is performed. This suggests that the circulating hormones, susceptible to be hydrolyzed by these enzymatic activities, are also modified.

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          Dysautonomia in Parkinson's disease: neurocardiological abnormalities.

          Symptoms of abnormal autonomic-nervous-system function occur commonly in Parkinson's disease (PD). Orthostatic hypotension in patients with parkinsonism has been thought to be a side-effect of treatment with levodopa, a late stage in the disease progression, or, if prominent and early with respect to disordered movement, an indication of a different disease, such as multiple system atrophy. Instead, patients with PD and orthostatic hypotension have clear evidence for baroreflex failure and loss of sympathetic innervation, most noticeably in the heart. By contrast, patients with multiple system atrophy, which is difficult to distinguish clinically from PD, have intact cardiac sympathetic innervation. Post-mortem studies confirm this distinction. Because PD involves postganglionic sympathetic noradrenergic lesions, the disease seems to be not only a movement disorder with dopamine loss in the nigrostriatal system of the brain, but also a dysautonomia, with norepinephrine loss in the sympathetic nervous system of the heart.
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            Alterations in angiotensin AT1 and AT2 receptor subtype levels in brain regions from patients with neurodegenerative disorders.

            The present studies assessed the levels of [125I][Sar1,ILE8]angiotensin II-labelled angiotensin AT1 and AT2 receptor recognition sites in homogenates of various brain areas (including caudate nucleus, putamen, substantia nigra, hippocampus, frontal cortex, temporal cortex and cerebellum) from patients with clinically diagnosed Parkinson's disease, Huntington's disease and Alzheimer's disease and those from age-, sex- and post-mortem delay-matched neurologically and psychiatrically normal patients. Radiolabelled angiotensin AT1 receptor recognition site levels were significantly decreased by approximately 70%, 70% and 90% in the caudate nucleus, putamen and substantia nigra, respectively, from patients with Parkinson's disease relative to matched controls. Furthermore, radiolabelled angiotensin AT2 receptor levels were decreased by some 60% in the caudate nucleus of patients with Parkinson's disease relative to control patients. In brain tissue homogenates from patients with Huntington's disease, the angiotensin AT1 receptor recognition site levels were decreased by approximately 30% in putamen relative to the control patients whilst angiotensin AT2 receptor levels were increased by some 90% in the caudate nucleus relative to the control patients. In brain tissue homogenates from patients with Alzheimer disease, the angiotensin AT2 receptor recognition site levels were significantly increased by approximately 200% in the temporal cortex relative to the control patients. The present results indicate that the reduction of angiotensin AT1 and/or AT2 receptor recognition site levels in the caudate nucleus, putamen and substantia nigra correlates with the principal neuropathology associated with Parkinson's disease and as such indicates that at least a significant population of angiotensin AT1 and AT2 receptors are located on the human dopaminergic nigrostriatal pathway. In addition, the marked increase in the levels of angiotensin AT2 receptor recognition sites in temporal cortex from patients with Alzheimer's disease correlates with some other markers associated with the renin-angiotensin system previously investigated in tissue from patients with this neurological disease.
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              Neuroendocrinology of ageing.

              Many common problems encountered in the ageing patient can be related to neuroendocrine phenomena. These include Alzheimer's disease, dementia and cognitive dysfunction, depression, Parkinson's disease, hyponatraemia and the postmenopausal increase in both vascular risk and osteoporosis. This review concentrates on the hypothalamic neuroendocrine system, including the dopaminergic, noradrenergic, serotoninergic, cholinergic and neurohypophyseal systems and the roles of the anterior pituitary and monoamine oxidases, luteinizing hormone-releasing hormone, corticotrophin-releasing factor, the pro-opiomelanocortin-derived and opioid peptides, peptides involved in growth hormone and thyrotropin regulation, and amino acid transmitters.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2004
                January 2005
                25 January 2005
                : 80
                : 4
                : 219-224
                Affiliations
                aUnit of Physiology, University of Jaén, Jaén, Spain; bInstituto de Neurociencias Federico Oloriz, Granada, Spain, and cMGConsulting Co, Rossemaison, Switzerland
                Article
                82748 Neuroendocrinology 2004;80:219–224
                10.1159/000082748
                15604601
                2af047d5-710b-4b46-bbca-897ebcc8820e
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 07 June 2004
                : 14 September 2004
                Page count
                Figures: 1, References: 34, Pages: 6
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Striatum,6-Hydroxydopamine,Aminopeptidases,Brain asymmetry,Parikinson’s disease

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