Linked Life Data

19596835

Source:http://linkedlifedata.com/resource/pubmed/id/19596835

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-9-22
pubmed:abstractText
We have shown that fluorescent, 7-nitro-2,1,3-benzoxadiazol-4-yl amino (NBD)-conjugated neurosteroid analogs photopotentiate GABA(A) receptor function. These compounds seem to photosensitize a modification of receptor function, resulting in long-lived increases in responses to exogenous or synaptic GABA. Here we extend this work to examine the effectiveness of different fluorophore positions, conjugations, steroid structures, and fluorophores. Our results are generally in agreement with the idea that steroids with activity at GABA(A) receptors are the most potent photopotentiators. In particular, we find that an unnatural enantiomer of an effective photopotentiating steroid is relatively weak, excluding the idea that membrane solubility alone, which is identical for enantiomer pairs, is solely responsible for potent photopotentiation. Furthermore, there is a significant correlation between baseline GABA(A) receptor activity and photopotentiation. Curiously, both sulfated steroids, which bind a presumed external neurosteroid antagonist site, and hydroxysteroids, which bind an independent site, are effective. We also find that a rhodamine dye conjugated to a 5beta-reduced 3alpha-hydroxy steroid is a particularly potent and effective photopotentiator, with minimal baseline receptor activity up to 10 muM. Steroid conjugated fluorescein and Alexa Fluor 546 also supported photopotentiation, although the Alexa Fluor conjugate was weaker and required 10-fold higher concentration to achieve similar potentiation to the best NBD and rhodamine conjugates. Filling cells with steroid-conjugated or free fluorophores via whole-cell patch pipette did not support photopotentiation. FM1-43, another membrane-targeted, structurally unrelated fluorophore, also produced photopotentiation at micromolar concentrations. We conclude that further optimization of fluorophore and carrier could produce an effective, selective, light-sensitive GABA(A) receptor modulator.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1521-0111
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
76
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
754-65
pubmed:dateRevised
2010-10-4
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Photodynamic effects of steroid-conjugated fluorophores on GABAA receptors.
pubmed:affiliation
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural