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Titolo:
Inhibition of synaptosomal uptake of H-3-L-glutamate and H-3-GABA by hyperforin, a major constituent of St. John's Wort: The role of amiloride sensitive sodium conductive pathways
Autore:
Wonnemann, M; Singer, A; Muller, WE;
Indirizzi:
Univ Frankfurt, Dept Pharmacol, Bioctr Niederusel, D-60439 Frankfurt, Germany Univ Frankfurt Frankfurt Germany D-60439 sel, D-60439 Frankfurt, Germany
Titolo Testata:
NEUROPSYCHOPHARMACOLOGY
fascicolo: 2, volume: 23, anno: 2000,
pagine: 188 - 197
SICI:
0893-133X(200008)23:2<188:IOSUOH>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT-BRAIN SYNAPTOSOMES; HYPERICUM EXTRACTS; NA+/H+ EXCHANGER; SEROTONIN UPTAKE; CLINICAL-TRIALS; ANTIDEPRESSANTS; PERFORATUM; DEPRESSION; BINDING; IDENTIFICATION;
Keywords:
hyperforin; St. John's Wort; amiloride sensitive sodium channel; Na+-H+ exchange; synaptosomal uptake inhibition;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Muller, WE Univ Frankfurt, Dept Pharmacol, Bioctr Niederusel, N260,Marie Curie Str 9,D-60439 Frankfurt, Germany Univ Frankfurt N260,Marie Curie Str 9Frankfurt Germany D-60439
Citazione:
M. Wonnemann et al., "Inhibition of synaptosomal uptake of H-3-L-glutamate and H-3-GABA by hyperforin, a major constituent of St. John's Wort: The role of amiloride sensitive sodium conductive pathways", NEUROPSYCH, 23(2), 2000, pp. 188-197

Abstract

Extracts of St. John's Wort are widely used for the treatment of depressive disorders. The active principles have not yet been finally elucidated. Wehave recently shown that hyperforin, a major active constituent of St. John's Wort, not only inhibits the neuronal uptake of serotonin, norepinephrine and dopamine, but also that of L-glutamate and GABA. No other antidepressant compound exhibits a similar broad uptake inhibiting profile. To investigate this unique kind of property, kinetic analyses were performed regarding the uptake of H-3-L-glutamate and H-3-GABA into Menten kinetics revealed a reduction of V-max (8.27 to 1.80 pmol/mg/min for H-3-L-glutamate, 2.76 to0.77 pmol/mg/min for H-3-GABA) while K-m was nearly unchanged in both cases, suggesting non-competitive inhibition. The unselective uptake inhibitionby hyperforin could be mimicked by the Na+-ionophore monensin and ny the Na+-K+-ATPase inhibitor ouabain. However, both mechanisms can be discarded for hyperforin. Several amiloride derivatives known to affect sodium conductance significantly enhance H-3-GABA and H-3-L-glutamate uptake and inhibit the uptake inhibition by hyperforin, while monensin or ouabain inhibition were not influenced. Selective concentrations of benzamil for amiloride sensitive Na+-channels and selective concentrations of 5'-ethylisopropylamiloride (EIPA) for the Na+-H+-exchangers both had an attenuating effect on the hyperforin inhibition of L-glutamate uptake, suggesting a possible role of amiloride sensitive Na+-channels and Na+-H+-exchangers in the mechanism of ation of hyperforin. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 09:06:53