Daniel J. Foster

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The CNS is particularly vulnerable to reductions in plasma osmolarity, such as occur during hyponatremia, the most commonly encountered electrolyte disorder in clinical practice. In response to a lowered plasma osmolarity, neural cells initially swell but then are able to restore their original volume through the release of osmolytes, both inorganic and(More)
The capacity of cells to correct their volume in response to hyposmotic stress via the efflux of inorganic and organic osmolytes is well documented. However, the ability of cell-surface receptors, in particular G-protein-coupled receptors (GPCRs), to regulate this homeostatic mechanism has received much less attention. Mechanisms that underlie the(More)
The ability of receptor activation to regulate osmosensitive K+ fluxes (monitored as 86Rb+) in SH-SY5Y neuroblastoma has been examined. Incubation of SH-SY5Y cells in buffers rendered increasingly hypotonic by a reduction in NaCl concentration resulted in an enhanced basal efflux of Rb+ (threshold of release, 200 mOsM) but had no effect on Rb(+) influx.(More)
The ability of prostanoid receptors to regulate the volume-dependent efflux of the organic osmolyte taurine from murine fibroblasts (L cells) via a cAMP-dependent mechanism has been examined. Incubation of L cells under hypoosmotic conditions resulted in a time-dependent efflux of taurine, the threshold of release occurring at 250 mOsM. Addition of(More)
Alzheimer's disease (AD) and schizophrenia (SZ) are neurological disorders with overlapping symptomatology, including both cognitive deficits and behavioral disturbances. Current clinical treatments for both disorders have limited efficacy accompanied by dose-limiting side effects, and ultimately fail to adequately address the broad range of symptoms(More)
The ability of G protein-coupled receptors to regulate osmosensitive uptake of the organic osmolyte, taurine, into human SH-SY5Y neuroblastoma cells has been examined. When monitored under isotonic conditions and in the presence of physiologically relevant taurine concentrations (1-100 microM), taurine influx was mediated exclusively by a Na(+)-dependent,(More)
Currently available therapeutic agents for treatment of schizophrenia target signaling by monoaminergic neurotransmitters; however, these treatments do not adequately treat the range of symptoms observed in patients. While these therapies treat the positive symptoms, they do not have efficacy in treating the negative symptoms and cognitive deficits that are(More)
Of the five muscarinic receptor subtypes, the M5 receptor is the only one detectable in midbrain dopaminergic neurons, making it an attractive potential therapeutic target for treating disorders in which dopaminergic signaling is disrupted. However, developing an understanding of the role of M5 in regulating midbrain dopamine neuron function has been(More)
Schizophrenia is associated with disruptions in N-methyl-D-aspartate glutamate receptor subtype (NMDAR)-mediated excitatory synaptic signaling. The metabotropic glutamate receptor subtype 5 (mGlu5) is a closely associated signaling partner with NMDARs and regulates NMDAR function in forebrain regions implicated in the pathology of schizophrenia. Efficacy of(More)
In addition to its function as an excitatory neurotransmitter, glutamate plays a major role as an osmolyte within the central nervous system (CNS). Accordingly, mechanisms that regulate glutamate release and uptake are of physiological importance not only during conditions in which cell volume remains constant but also when cells are subjected to(More)