| Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus. | |
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MedLine Citation:
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PMID: 18094067 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Brain catecholamines are involved in the regulation of biological functions, including cardiovascular activity. The hypothalamus presents areas with high density of catecholaminergic neurons and the endothelin system. Two hypothalamic regions intimately related with the cardiovascular control are distinguished: the anterior (AHR) and posterior (PHR) hypothalamus, considered to be sympathoinhibitory and sympathoexcitatory regions, respectively. We previously reported that endothelins (ETs) are involved in the short-term tyrosine hydroxylase (TH) regulation in both the AHR and PHR. TH is crucial for catecholaminergic transmission and is tightly regulated by well-characterized mechanisms. In the present study, we sought to establish the effects and underlying mechanisms of ET-1 and ET-3 on TH long-term modulation. Results showed that in the AHR, ETs decreased TH activity through ET(B) receptor activation coupled to the nitric oxide, phosphoinositide, and CaMK-II pathways. They also reduced total TH level and TH phosphorylated forms (Ser 19 and 40). Conversely, in the PHR, ETs increased TH activity through a G protein-coupled receptor, likely an atypical ET receptor or the ET(C) receptor, which stimulated the phosphoinositide and adenylyl cyclase pathways, as well as CaMK-II. ETs also increased total TH level and the Ser 19, 31, and 40 phosphorylated sites of the enzyme. These findings support that ETs are involved in the long-term regulation of TH activity, leading to reduced sympathoinhibition in the AHR and increased sympathoexcitation in the PHR. Present and previous studies may partially explain the cardiovascular effects produced by ETs when applied to the brain. |
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Authors:
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Guadalupe Perfume; Sabrina L Nabhen; Karla Riquelme Barrera; María G Otero; Liliana G Bianciotti; Marcelo S Vatta |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-12-19 |
Journal Detail:
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Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 294 ISSN: 0363-6119 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-03-04 Completed Date: 2008-10-31 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: United States |
Other Details:
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Languages: eng Pagination: R905-14 Citation Subset: IM |
Affiliation:
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Cátedra de Fisiología, Instituto de Química y Metabolismo del Fármaco, Consejo Nacional de Investigaciones Cientifica y Técnicas, Buenos Aires, Argentina. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenylate Cyclase
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physiology Animals Blotting, Western Calcium-Calmodulin-Dependent Protein Kinase Type 2 / physiology Cyclic AMP-Dependent Protein Kinases / physiology Endothelin-1 / pharmacology* Endothelin-3 / pharmacology* Hypothalamus, Anterior / drug effects*, enzymology* Hypothalamus, Posterior / drug effects*, enzymology* Male Nitric Oxide / physiology Phosphatidylinositols / physiology Phosphorylation Rats Rats, Sprague-Dawley Receptor, Endothelin B / drug effects Receptors, G-Protein-Coupled / drug effects Signal Transduction / drug effects Suramin / pharmacology Tyrosine 3-Monooxygenase / biosynthesis*, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Endothelin-1; 0/Endothelin-3; 0/Phosphatidylinositols; 0/Receptor, Endothelin B; 0/Receptors, G-Protein-Coupled; 10102-43-9/Nitric Oxide; 145-63-1/Suramin; EC 1.14.16.2/Tyrosine 3-Monooxygenase; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinase Type 2; EC 4.6.1.1/Adenylate Cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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