| Signal transduction alterations in peripheral nerves from streptozotocin-induced diabetic rats. | |
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MedLine Citation:
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PMID: 7473883 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have previously determined the presence of muscarinic receptors and the expression of several G proteins in homogenates and myelin fractions from rat sciatic nerves. In the present study we investigated whether changes in several signal transduction pathways in peripheral nerves might be responsible for some of the biochemical abnormalities (e.g., phosphoinositide metabolism) present in sciatic nerves from streptozotocin-induced diabetic rats. Sciatic nerves from 5 week diabetic rats that were prelabelled with [3H]-myo-inositol displayed a significant increase in the basal release of inositol mono- and bis-phosphate, while carbamylcholine-stimulated release was significantly smaller. Basal- and forskolin-stimulated adenylyl cyclase activity was significantly decreased in sciatic nerve homogenates from diabetic animals. However, we were unable to detect any significant differences in the levels of cAMP in intact nerves or in nerve segments that were incubated in the presence or absence of forskolin. ADP-ribosylation experiments showed that in sciatic nerves from experimentally diabetic rats there was a significant increase in the ADP-ribosylation catalyzed by cholera and pertussis toxins. Measurements of the levels of alpha-subunits of G proteins revealed that the expression of Gq/11 alpha, Gs alpha, and Gi-3 alpha was increased by 30 to 50%. These results indicate that during the course of experimental diabetes, peripheral nerves exhibit an abnormal production of inositol phosphates and cAMP, together with an abnormal expression and/or function of G proteins. One of the consequences of such alterations is the diminished release of inositol phosphates triggered by muscarinic agonists in diabetic sciatic nerves. |
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Authors:
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T Y Goraya; P Wilkins; J G Douglas; J Zhou; L N Berti-Mattera |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of neuroscience research Volume: 41 ISSN: 0360-4012 ISO Abbreviation: J. Neurosci. Res. Publication Date: 1995 Jul |
Date Detail:
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Created Date: 1995-11-24 Completed Date: 1995-11-24 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7600111 Medline TA: J Neurosci Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 518-25 Citation Subset: IM |
Affiliation:
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Department of Medicine, University Hospitals of Cleveland, Ohio, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenylate Cyclase
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metabolism Animals Cyclic AMP / metabolism Diabetes Mellitus, Experimental Disease Models, Animal Forskolin / pharmacology Male Peripheral Nervous System Rats Rats, Sprague-Dawley Sciatic Nerve / metabolism* Signal Transduction* Streptozocin / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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DK 44097/DK/NIDDK NIH HHS; HL 22990/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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18883-66-4/Streptozocin; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; EC 4.6.1.1/Adenylate Cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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