Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.107 (DAT)
 1,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HIV-associated neurocognitive disorder (HAND) remains highly prevalent in HIV infected individuals and represents a special group of neuropathological disorders, which are associated with HIV-1 viral proteins, such as transactivator of transcription (Tat) protein. Cocaine abuse increases the incidence of HAND and exacerbates its severity by enhancing viral replication. Perturbation of dopaminergic transmission has been implicated as a risk factor of HAND. The presynaptic dopamine (DA) transporter (DAT) is essential for DA homeostasis and dopaminergic modulation of the brain function including cognition. Tat and cocaine synergistically elevate synaptic DA levels by acting directly on human DAT (hDAT), ultimately leading to dysregulation of DA transmission. Through integrated computational modeling and experimental validation, key residues have been identified in hDAT that play a critical role in Tat-induced inhibition of DAT and induce transporter conformational transitions. This review presents current information regarding neurological changes in DAT-mediated dopaminergic system associated with HIV infection, DAT-mediated adaptive responses to Tat as well as allosteric modulatory effects of novel compounds on hDAT. Understanding the molecular mechanisms by which Tat induces DAT-mediated dysregulation of DA system is of great clinical interest for identifying new targets for an early therapeutic intervention for HAND.
 ...
PMID:The role of human dopamine transporter in NeuroAIDS. 2898 21

The mesolimbic dopamine system is important for reward-oriented behaviours, such as drinking and eating. However, the precise involvement of dopaminergic neurons and dopamine receptors in water drinking behaviour remains unclear. Here, we generated triple transgenic mice harbouring Slc6a3(DAT)-icre/ERT2, Camk2a-loxP-STOP-loxP-tetracycline transactivator and tetO-tetanus toxin constructs, in which the release of dopamine is blocked by tetanus toxin. These mice, referred to as dopamine secretion interference mice, had reduced dopamine secretion in the striatum (61.4%) and the nucleus accumbens (54.5%). They showed adequate limb strength and food consumption, similarly to control mice, but exhibited motor control impairment in a challenging rotarod test. Dopamine secretion interference mice made fewer licks and had fewer bursts than control mice during a licking test under thirsty conditions. To elucidate the influence of dopamine receptors in the altered drinking behaviour, a dopamine D1 or D2/D3 receptor agonist (A68930 or ropinirole, respectively) was administered prior to the licking microstructure analysis. Treatment with the D1 agonist restored the total number of licks but not the burst number in dopamine secretion interference mice. By contrast, the D2/3 agonist impeded water drinking behaviour in both transgenic and control mice. The present findings indicate that D1 receptor activation partially ameliorates the altered drinking behaviour of the dopamine secretion interference mice and suggest that D1 receptor activity impacts drinking under thirsty conditions.
 ...
PMID:Differential effects of dopamine D1-like and D2-like receptor agonists on water drinking behaviour under thirsty conditions in mice with reduced dopamine secretion. 3147 80