Document Detail


Regulation of neurosteroid allopregnanolone biosynthesis in the rat spinal cord by glycine and the alkaloidal analogs strychnine and gelsemine.
MedLine Citation:
PMID:  18367344     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The neurosteroid allopregnanolone (3alpha,5alpha-THP) is well characterized as a potentially therapeutic molecule which exerts important neurobiological actions including neuroprotective, antidepressant, anxiolytic, anesthetic and analgesic effects. We have recently observed that neurons and glial cells of the rat spinal cord (SC) contain various key steroidogenic enzymes such as 5alpha-reductase and 3alpha-hydroxysteroid oxido-reductase which are crucial for 3alpha,5alpha-THP biosynthesis. Furthermore, we demonstrated that the rat SC actively produces 3alpha,5alpha-THP. As the key factors regulating neurosteroid production by nerve cells are unknown and because glycine is one of the pivotal inhibitory neurotransmitters in the SC, we investigated glycine effects on 3alpha,5alpha-THP biosynthesis in the rat SC. Glycine markedly stimulated [(3)H]-progesterone conversion into [(3)H]3alpha,5alpha-THP by SC slices. The alkaloid strychnine, well-known as a glycine receptor (Gly-R) antagonist, blocked glycine stimulatory effect on 3alpha,5alpha-THP formation. Gelsemine, another alkaloid containing the same functional groups as strychnine, increased 3alpha,5alpha-THP synthesis. The stimulatory effects of glycine and gelsemine on 3alpha,5alpha-THP production were additive when the two drugs were combined. These results demonstrate that glycine and gelsemine, acting via Gly-R, upregulate 3alpha,5alpha-THP biosynthesis in the SC. The data also revealed a structure-activity relationship of the analogs strychnine and gelsemine on neurosteroidogenesis. Possibilities are opened for glycinergic agents and gelsemine utilization to stimulate selectively 3alpha,5alpha-THP biosynthetic pathways in diseases evoked by a decreased neurosteroidogenic activity of nerve cells.
Authors:
C Venard; N Boujedaini; P Belon; A G Mensah-Nyagan; C Patte-Mensah
Related Documents :
1874974 - Appearance of cytokine-associated central nervous system myelin damage coincides tempor...
18367344 - Regulation of neurosteroid allopregnanolone biosynthesis in the rat spinal cord by glyc...
11874204 - Immunohistochemical study of immunophilin 1-15 fragment in intact frog brain, and in th...
10407104 - Immunohistochemical localization of connective tissue growth factor in the rat central ...
9887194 - Impaired autoregulation of renal blood flow in the fawn-hooded rat.
168064 - Attempts to produce spike-and-wave complexes in the electrocorticogram of the rat.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-02-19
Journal Detail:
Title:  Neuroscience     Volume:  153     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-21     Completed Date:  2008-08-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  154-61     Citation Subset:  IM    
Affiliation:
Equipe Stéroïdes et Système Nociceptif, Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique/Université Louis Pasteur, 21 rue René Descartes, 67084 Strasbourg Cedex, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Alkaloids / chemistry,  pharmacology*
Animals
Dose-Response Relationship, Drug
Drug Antagonism
Drug Synergism
Glycine / pharmacology,  physiology*
Glycine Agents / chemistry,  pharmacology
Male
Molecular Structure
Neuroglia / drug effects,  metabolism
Neurons / drug effects,  metabolism
Organ Culture Techniques
Pregnanolone / biosynthesis*
Rats
Rats, Sprague-Dawley
Receptors, Glycine / drug effects*,  metabolism
Spinal Cord / drug effects*,  metabolism
Strychnine / chemistry,  pharmacology*
Chemical
Reg. No./Substance:
0/Alkaloids; 0/Glycine Agents; 0/Receptors, Glycine; 128-20-1/Pregnanolone; 509-15-9/gelsemine; 56-40-6/Glycine; 57-24-9/Strychnine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Primate-like retinotectal decussation in an echolocating megabat, Rousettus aegyptiacus.
Next Document:  Enhancing prediction of inhalant abuse risk in samples of early adolescents: a secondary analysis.