Zusammenfassung
Ähnlich wie die Elektrolyt-Homöostase ist auch der intrazelluläre pH-Wert (pHi) von
Neuronen besonders intensiv kontrolliert. Dieses geschieht beispielsweise durch spezielle
membranständige Systeme, die Säureäquivalente in die Zelle hinein und wieder heraus
transportieren können. Die Regulation des pHi dient unter anderem der Steuerung der
neuronalen Erregbarkeit, da eine Erregbarkeitssteigerung in den meisten Neuronen den
pHi senkt und vice versa eine intrazelluläre Azidose im Sinne einer negativen Rückkopplungs-Schleife
die Erregbarkeit wieder senkt. Änderungen des pHi haben darüber hinaus Einflüsse auf
beinahe jede Zellfunktion. Da über die Wirkung von Neuropsychopharmaka auf die H + -Homöostase wenig bekannt ist, untersuchten wir diesbezüglich mehrere Antipsychotika,
Antidepressiva, Antikonvulsiva und Lithium. Als Modell wurden hippocampale CA 3-Neurone
in Gewebeschnitten (vom Meerschweinchen) eingesetzt, die mit dem intrazellulären pHi-Indikator
BCECF gefärbt worden waren. In therapeutischen und supratherapeutischen Konzentrationen
veränderten alle gemessenen Antipsychotika, die meisten Antidepressiva und gut die
Hälfte aller untersuchten Antikonvulsiva reversibel den pHi dieser Neurone. Obwohl
diesbezüglich noch bestätigende In-vivo-Experimente fehlen, möchten wir auf die mögliche
pHi-Aktivität von Neuropsychopharmaka aufmerksam machen, insbesondere, wenn deren
therapeutische oder toxische Wirkungen diskutiert werden.
Abstract
The intracellular pH (pHi) of neurons is tightly regulated, mainly by membrane-bound
transporters acting as acid extruders or acid loaders. Regulation of pHi helps to
control neuronal excitability, as increased bioelectric activity moderately lowers
pHi and, in the sense of a negative feedback loop, intracellular acidosis mostly reduces
neuronal excitability. Moreover, a change of pHi widely influences complex cellular
functions. With respect to neuropsychopharmaca, little is known about whether or not
they may affect neuronal H + -homeostasis. To this aim, we tested several antipsychotics, antidepressants, anticonvulsants,
and lithium for effects on neuronal pHi, using guinea pig hippocampal slice preparations
in which CA 3 pyramidal neurons were loaded with the pHi-sensitive dye BCECF-AM. All
antipsychotics, most antidepressants and about half of the anticonvulsants tested
so far elicited reversible changes of neuronal pHi when applied at therapeutic and
supratherapeutic concentrations. Although these results await confirmatory in vivo
experiments, we believe that the pHi activity of neuropsychopharmaca needs further
attention, especially when therapeutic mechanisms or even harmful side effects are
discussed.
Schlüsselwörter
intrazellulärer pH - Neuropsychopharmaka - pH-Regulation
Keywords
intracellular pH - neuropsychopharmaca - pH regulation
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Prof. Dr. med. Udo Bonnet
Klinik für Psychiatrie und Psychotherapie Evangelisches Krankenhaus Castrop-Rauxel,
Akademisches Lehrkrankenhaus der Universität Duisburg-Essen
Grutholzallee 21
44577 Castrop-Rauxel
Email: u.bonnet@evk-castrop-rauxel.de
