Ascorbate Modulates 5‐[³H]Hydroxytryptamine Binding to Central 5‐HT₃ Sites in Bovine Frontal Cortex

Abstract

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.

Effect of Supplementation of Vitamin E and Vitamin C on Brain Acetylcholinesterase Activity and Neurotransmitter Levels in Rats Treated with Scopolamine, an Inducer of Dementia.

“…This may be ex plained by the study of Todd and Bauer (40) that vita min C may modulate the serotonergic function by con trolling 5-[3H]-hydroxytryptamine binding to bovine frontal cortex membranes. From the findings of our study and others (20,40), it appeared that vitamin C supplementation might have a beneficial effect on pre venting damage to the nervous system. More elaborated studies are needed to investigate the effects of vitamin C or vitamin E supplementation on brain neurotransmit ter metabolism.…”

Effect of acute and chronic MK-801 administration on extracellular glutamate and ascorbic acid release in the prefrontal cortex of freely moving mice on line with open-field behavior

“…Ascorbic acid (AA), a water-soluble vitamin, a potentially important modulator of brain function, is known for its antioxidant properties (Halliwell, 1996;Rice, 2000), may play an important role in the development of schizophrenia. Additionally, AA can block a variety of membrane bound receptor proteins including the NMDA site (Majewska et al, 1990), as well as adrenergic, serotonergic and dopaminergic receptors (Jones and Bylund, 1986;Kaylaap et al, 1981;Todd and Bauer, 1988) and inhibit binding of ( 3 H) Glu to the NMDA receptor complex and reduces NMDA-gated currents in isolated neurons (Majewska et al, 1990). Many experimental evidences suggest that AA plays a key role in modulating central dopaminergic (Rebec and Pierce, 1994) and glutamatergic transmission (Miele et al, 1994;Rebec and Pierce, 1994;Miele et al, 1995) as well as behavior (Miele et al, 1995;De Angeli, 1995).…”

Ascorbic acid transport in mouse and rat astrocytes is reversibly inhibited by furosemide, SITS, and DIDS

“…Ascorbic acid (vitamin C) is absorbed by the intestine or synthesized by the liver and then delivered through the bloodstream to the brain (1,2). The vitamin is essential for brain function because it is a cofactor in catecholamine biosynthesis (3), facilitiates release of transmitters (4)(5)(6), modulates binding of ligands to neural receptors (7)(8)(9), and slows rates of transmitter clearance (10)(11)(12). There is evidence that ascorbate is actively transported in rat cerebral cortex (13) and that brain cells regulate the extracellular concentration of vitamin C (14).…”