Linked Life Data

11518080

Source:http://linkedlifedata.com/resource/pubmed/id/11518080

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2001-8-23
pubmed:abstractText
Hyperforin, an acylphloroglucinol derivative, is a major constituent of St. John's wort extract (Hypericum perforatum L.), which is used in treating depressive disorders. Hyperforin has been demonstrated as a modulator of several neuronal ion channels, and inhibits smooth-muscle contraction induced by various neurotransmitters. To evaluate the spasmolytic properties of hyperforin in more detail, we performed studies on the hamster vas deferens smooth muscle cell line DDT1-MF2. In a first series of experiments, we determined the effect of hyperforin on intracellular Ca2+ concentration ([Ca2+]i) using the fluorochrome fura-2. These investigations were supplemented in a second series of assays, where the effects on cellular metabolism were analysed by measuring the rate of extracellular release of acidic metabolites with the help of a microphysiometer. Hyperforin (0.3-10 microg/ml) caused a concentration-dependent elevation of [Ca2+]i and extracellular acidification rate (ECAR). Both of these effects were independent of extracellular Ca2+. To elucidate whether the increase of [Ca2+]i by hyperforin causes or results from its ECAR-stimulating properties, we used various pharmacological tools to reveal the sequence of events and the molecular mechanisms involved. Our results suggest that hyperforin induces release of Ca2+ from as yet unidentified sources. Since the ECAR stimulation was inhibited to a different extent by the intracellular Ca2+ chelator BAPTA as well as by inhibitors of plasmalemmal and mitochondrial Na+/Ca2+ exchange, but not by inhibitors of Na+/H+ antiport, the intracellular Ca2+ increase seems to be essential for this hyperforin effect. However, further studies are needed to establish the exact mode of action, and to deduce whether this aspect of hyperforin activity contributes to its antidepressant and neuroprotective effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0176-3679
pubmed:author
pubmed:issnType
Print
pubmed:volume
34 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S70-3
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Hyperforin stimulates intracellular calcium mobilisation and enhances extracellular acidification in DDT1-MF2 smooth muscle cells.
pubmed:affiliation
Department of Pharmacology, Dr. Willmar Schwabe GmbH & Co., Arzneimittel, Karlsruhe, Germany.
pubmed:publicationType
Journal Article