Linked Life Data

11599300

Source:http://linkedlifedata.com/resource/pubmed/id/11599300

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2001-10-15
pubmed:abstractText
Certain pregnane steroids are now established as potent, positive allosteric modulators of the gamma-aminobutyric acid type A (GABAA) receptor. These compounds are known to be synthesized in the periphery by endocrine glands, such as the ovaries and the adrenal glands, and can rapidly cross the blood-brain barrier. Therefore, such steroids could act as endogeneous modulators of the major inhibitory receptor in the mammalian central nervous system. However, the demonstration that certain neurons and glia can synthesize the pregnane steroids (i.e., neurosteroids) additionally suggests that they may serve a paracrine role by influencing GABAA-receptor function through their local release in the brain itself. Here, we demonstrate that these neurosteroids are highly selective and extremely potent modulators of the GABAA receptor. The subunit composition of the GABAA receptor may influence the actions of the neurosteroids, particularly when considering concentrations of these agents thought to occur physiologically, which may underlie their reported differential effects at certain inhibitory synapses. However, recent work suggests that the phosphorylation status of either the synaptic GABAA receptor or its associated proteins may also influence neurosteroid sensitivity; these findings are discussed. Upon administration, the neurosteroids exhibit clear behavioral effects, including sedation, anticonvulsant actions, and behaviors predictive of anxiolysis; when given at high doses, they induce general anesthesia. Numerous synthetic steroids have been synthesized in an attempt to therapeutically exploit these properties, and these data are reviewed in this chapter. However, targeting the brain enzymes that synthesize and metabolize the neurosteroids may offer a new approach to exploit this novel endocrine-paracrine neurotransmitter interaction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0074-7742
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
177-205
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Neurosteroid modulation of recombinant and synaptic GABAA receptors.
pubmed:affiliation
Department of Pharmacology and Neuroscience, Ninewells Hospital and Medical School, Dundee University, Dundee, DD1 9SY Scotland.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't