Publications by authors named "Vanaja Jaligam"

Article Synopsis
  • Salvinorin A (SalA) is a selective κ-opioid receptor agonist that leads to dysphoria and depressive-like effects, mainly by inhibiting dopamine release.
  • SalA activates dopamine transporters (DAT) and forms complexes with κ-opioid receptors (KOR), enhancing DAT function while decreasing serotonin transporter (SERT) activity.
  • The interaction between DAT and KOR, mediated by the ERK1/2 signaling pathway, suggests that the overall increase in DAT activity and decrease in dopamine signaling contribute to the negative mood effects associated with SalA.
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The serotonin transporter (SERT) mediates clearance of serotonin from the synapse, thereby, regulating extracellular serotonin concentrations. Radioligand uptake techniques are typically used to assess SERT function in tissue and heterologous expression systems. The need for sufficient protein in samples, however, requires use of homogenate preparations, potentially masking effects limited to specific cell populations.

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The endocannabinoid, anandamide (AEA), modulates the activity of the dopamine transporter (DAT) in heterologous cells and synaptosomal preparations. The cellular mechanisms mediating this effect are unknown. The present studies employed live cell imaging techniques and the fluorescent, high affinity DAT substrate, 4-(4-(dimethylamino)-styryl)-N-methylpyridinium (ASP(+)), to address this issue.

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D(3) dopamine receptors are expressed by dopamine neurons and are implicated in the modulation of presynaptic dopamine neurotransmission. The mechanisms underlying this modulation remain ill defined. The dopamine transporter, which terminates dopamine transmission via reuptake of released neurotransmitter, is regulated by receptor- and second messenger-linked signaling pathways.

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Article Synopsis
  • The dopamine transporter (DAT) is responsible for reabsorbing dopamine from the neurotransmission process, and its regulation by D(2) dopamine receptors (D(2)R) has been found to be complex due to the high affinity of dopamine for these receptors.
  • Using live cell imaging with a fluorescent DAT substrate, researchers studied the impact of D(2)R-linked signaling pathways (ERK1/2 and PI3K) on DAT regulation.
  • Results indicated that activating the D(2)R increased DAT expression on the cell surface and enhanced dopamine uptake, primarily through a mechanism dependent on ERK1/2 rather than PI3K, suggesting a potential interaction between DAT and D(2)R.
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