Ascorbate modulates 5-[3H]hydroxytryptamine binding to central 5-HT3 sites in bovine frontal cortex.
Ascorbate is present in millimolar concentrations in mammalian brain and can be released from cellular stores by membrane depolarization. We report here that physiologically relevant concentrations of ascorbate modulate 5-[3H]hydroxytryptamine ([3H]5-HT) binding to bovine frontal cortex membranes. Under conditions where [3H]5-HT binding is reversible and saturable, ascorbate causes a concentration-dependent increase in the affinity of [3H]5-HT for central 5-HT3 binding sites. At pH 7.4, increasing ascorbate from 0 to 5.7 mM changes the equilibrium affinity constant (KD) of binding to 5-HT3 sites from 125 nM to 30 nM, without affecting binding site number. These ascorbate-induced effects are pH dependent. At pH 7.1 binding to central 5-HT3 sites is essentially eliminated in the presence of ascorbate. These studies suggest that ascorbate and hydrogen ion concentration interactions may modulate serotonergic function.
Todd
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RD
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110.
Bauer
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PA
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
D011985:Receptors, Serotonin; D012701:Serotonin; D001205:Ascorbic Acid