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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1989-1-25
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pubmed:abstractText |
Corticotropin-releasing hormone (CRH) has been considered a major coordinator of the overall physical and behavioral response to stress. Moreover, prolonged hypersecretion of CRH has been implicated in the pathogenesis of disorders characterized by anxiety and/or depression. Drugs acting through the gamma-aminobutyric acid/benzodiazepine (GABA/BZD) receptor system have anxiolytic and/or antidepressant properties whereas benzodiazepine inverse agonists cause anxiety and stimulate the pituitary-adrenal axis in vivo. To examine the involvement of the GABA/BZD system in the regulation of hypothalamic CRH secretion, we studied the effects of various agonists and antagonists of GABAA and GABAB receptors using a sensitive rat hypothalamic organ culture with radioimmunoassayable CRH (IR-rCRH) as endpoint. The GABAA and GABAB receptor agonist GABA inhibited serotonin (5-HT)-induced IR-rCRH secretion from 10(-9) to 10(-6) M, but failed to do so at 10(-5) M. The GABAA receptor agonist muscimol was a weak inhibitor of 5-HT-induced IR-rCRH secretion, being effective only at the concentration of 10(-6) M. In contrast, the specific GABAB receptor agonist baclofen was able to inhibit 5-HT-induced IR-rCRH secretion from 10(-7) to 10(-5) M. The rank of potency was thus, GABA much greater than baclofen greater than muscimol. Bicuculline, a GABAA receptor antagonist, partially reversed the inhibitory effects of GABA. Diazepam, a classic benzodiazepine which interacts with the benzodiazepine-site of the GABAA receptor complex, inhibited 5-HT-induced IR-rCRH secretion from 3.3 X 10(-9) to 10(-5) M, an effect that could be reversed by the BZD inactive ligand Ro15-1788.(ABSTRACT TRUNCATED AT 250 WORDS)
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Baclofen,
http://linkedlifedata.com/resource/pubmed/chemical/Corticotropin-Releasing Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Diazepam,
http://linkedlifedata.com/resource/pubmed/chemical/Muscimol,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/gamma-Aminobutyric Acid
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0006-8993
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
463
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
28-36
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:3264201-Animals,
pubmed-meshheading:3264201-Baclofen,
pubmed-meshheading:3264201-Corticotropin-Releasing Hormone,
pubmed-meshheading:3264201-Diazepam,
pubmed-meshheading:3264201-Hypothalamus,
pubmed-meshheading:3264201-Male,
pubmed-meshheading:3264201-Muscimol,
pubmed-meshheading:3264201-Organ Culture Techniques,
pubmed-meshheading:3264201-Rats,
pubmed-meshheading:3264201-Rats, Inbred Strains,
pubmed-meshheading:3264201-Serotonin,
pubmed-meshheading:3264201-gamma-Aminobutyric Acid
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pubmed:year |
1988
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pubmed:articleTitle |
Interaction between GABAergic neurotransmission and rat hypothalamic corticotropin-releasing hormone secretion in vitro.
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pubmed:affiliation |
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892.
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pubmed:publicationType |
Journal Article,
In Vitro
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