| Experimental uremia affects hypothalamic amino acid neurotransmitter milieu. | |
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MedLine Citation:
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PMID: 11373345 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chronic renal failure is associated with delayed puberty and hypogonadism. To investigate the mechanisms subserving the reported reduced pulsatile release of gonadotropin-releasing hormone (GnRH) in chronic renal failure, this study examined the amino acid neurotransmitter milieu in the medial preoptic area (MPOA), the hypothalamic region where the GnRH-secreting neurons reside, in 5/6-nephrectomized male rats and in ad libitum-fed or pair-fed controls. All rats were castrated and received either a testosterone or a vehicle implant to evaluate additional effects of the prevailing sex steroid milieu. Local excitatory (essential amino acids: aspartate, glutamate) and inhibitory (gamma-aminobutyric acid [GABA], taurine) amino acid transmitter outflow in the MPOA was measured by microdialysis via stereotactically implanted cannulae in the awake, freely moving rats. In addition to basal extracellular concentrations, the neurosecretory capacity was assessed by the addition of 100 mM KCl to the dialysis fluid. The mechanisms of neurosecretion were evaluated further by inhibition of vesicular release with the use of Ca(2+)-free, Mg(2+)-enriched dialysis fluid and by local perfusion with inhibitors of voltage-dependent synaptic release (1 microM tetrodotoxin) and of GABA reuptake (0.5 mM nipecotic acid). In the uremic rats, basal outflow of GABA, glutamate and aspartate, and K(+)-stimulated aspartate outflow were increased. K(+)-stimulated GABA and glutamate release was less sensitive to Ca(2+) depletion in the uremic than in the control rats. The elevated basal GABA and essential amino acid outflow in the uremic rats was due to a voltage- and Ca(2+)-independent mechanism. GABA reuptake was inhibited proportionately by nipecotic acid in uremic and pair-fed control rats. Testosterone supplementation had no independent effects on neurotransmitter outflow. In summary, the amino acid neurotransmitter milieu is altered in the MPOA of uremic rats by a nonsynaptic, nonvesicular mechanism. These abnormalities may contribute to the impaired function of the GnRH pulse generator. |
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Authors:
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F Schaefer; M Vogel; G Kerkhoff; J Woitzik; M Daschner; O Mehls |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of the American Society of Nephrology : JASN Volume: 12 ISSN: 1046-6673 ISO Abbreviation: J. Am. Soc. Nephrol. Publication Date: 2001 Jun |
Date Detail:
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Created Date: 2001-05-24 Completed Date: 2001-08-02 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9013836 Medline TA: J Am Soc Nephrol Country: United States |
Other Details:
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Languages: eng Pagination: 1218-27 Citation Subset: IM |
Affiliation:
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Division of Paediatric Nephrology, University Children's Hospital, University of Heidelberg, Heidelberg, Germany. franz_schaefer@med.uni-heidelberg.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids
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metabolism* Analysis of Variance Animals Disease Models, Animal Gonadotropin-Releasing Hormone / metabolism* Hypothalamus / metabolism Male Microdialysis Neurotransmitter Agents / metabolism* Rats Rats, Sprague-Dawley Tetrodotoxin / pharmacology Uremia / physiopathology* gamma-Aminobutyric Acid / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Neurotransmitter Agents; 33515-09-2/Gonadotropin-Releasing Hormone; 4368-28-9/Tetrodotoxin; 56-12-2/gamma-Aminobutyric Acid |
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