Linked Life Data

10454515

Source:http://linkedlifedata.com/resource/pubmed/id/10454515

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-9-21
pubmed:abstractText
Extracts of Hypericum perforatum (St. John's Wort) are widely used for the treatment of depressive disorders and are unspecific inhibitors of the neuronal uptake of several neurotransmitters. Previous studies have shown that hyperforin represents the reuptake inhibiting constituent. To characterize the mechanism of serotonin reuptake inhibition, kinetic analyses in synaptosomes of mouse brain were performed. Michaelis-Menten kinetics revealed that hyperforin (2 microM) induces a decrease in V(max) by more than 50% while only slightly decreasing K(m), indicating mainly noncompetitive inhibition. By contrast, citalopram (1 nM) leads to an elevation of K(m) without changing V(max). Monensin, a Na(+)/H(+) exchanger, showed similar properties as hyperforin (decrease of V(max) without changing K(m)). Compared with classical antidepressants, such as selective serotonin reuptake inhibitors and tricyclic antidepressants, hyperforin is only a weak inhibitor of [(3)H]paroxetine binding relative to its effects on serotonin uptake. As monensin decreases serotonin uptake by increasing Na(+)/H(+) exchange, we compared the effects of hyperforin and monensin on the free intracellular sodium concentration ([Na(+)](i)) in platelets by measuring 1,3-benzenedicarboxylic acid, 4,4'-[1,4,10-trioxa-7, 13-diazacyclopentadecan-7,13-diylbis(5-methoxy-6, 2-benzofurandiyl)]bis-, tetraammonium salt (SBFI/AM) fluorescence. Both drugs elevated [Na(+)](i) over basal levels, with a maximal [Na(+)](i) of 69 +/- 16.1 mM (50 microM hyperforin) and 140 +/- 9.1 mM (10 microM monensin). Citalopram at concentrations relevant for [(3)H]serotonin uptake inhibition had no effect on [Na(+)](i). Although the mode of action of hyperforin seems to be associated with elevated [Na(+)](i) similar to those levels found with monensin, the molecular mechanism might be different, as even at high concentrations, hyperforin does not elevate free intracellular sodium concentration ([Na(+)](i)) up to the extracellular level, as monensin does. Hyperforin represents the first substance with a known preclinical antidepressant profile that inhibits serotonin uptake by elevating [Na(+)](i).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
290
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1363-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10454515-Animals, pubmed-meshheading:10454515-Antidepressive Agents, pubmed-meshheading:10454515-Bicyclo Compounds, pubmed-meshheading:10454515-Binding, Competitive, pubmed-meshheading:10454515-Binding Sites, pubmed-meshheading:10454515-Brain, pubmed-meshheading:10454515-Female, pubmed-meshheading:10454515-Humans, pubmed-meshheading:10454515-Intracellular Fluid, pubmed-meshheading:10454515-Kinetics, pubmed-meshheading:10454515-Mice, pubmed-meshheading:10454515-Paroxetine, pubmed-meshheading:10454515-Phloroglucinol, pubmed-meshheading:10454515-Plant Extracts, pubmed-meshheading:10454515-Serotonin, pubmed-meshheading:10454515-Serotonin Uptake Inhibitors, pubmed-meshheading:10454515-Sodium, pubmed-meshheading:10454515-Synaptosomes, pubmed-meshheading:10454515-Terpenes, pubmed-meshheading:10454515-Theales, pubmed-meshheading:10454515-Tritium
pubmed:year
1999
pubmed:articleTitle
Hyperforin, a major antidepressant constituent of St. John's Wort, inhibits serotonin uptake by elevating free intracellular Na+1.
pubmed:affiliation
Department of Pharmacology, Biocenter, University of Frankfurt, Frankfurt, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't