Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Negative regulation of neuronal serotonin (5-HT1A) receptor levels by glucocorticoids in vivo may contribute to depression. Both types I (mineralocorticoid) and II (glucocorticoid) receptors (MR and GR, respectively) participate in corticosteroid-induced transcriptional repression of the 5-HT1A gene; however, the precise mechanism is unclear. A direct repeat 6-base pair glucocorticoid response element (GRE) half-site 5'-TGTCCT separated by 6 nucleotides was conserved in human, mouse, and rat 5-HT1A receptor promoters. In SN-48 neuronal cells that express MR, GR, and 5-HT1A receptors, deletion or inactivation of the nGRE (negative GRE) eliminated negative regulation of the rat 5-HT1A or heterologous promoters by corticosteroids, whereas its inclusion conferred corticosteroid-induced inhibition to a heterologous promoter. Bacterially expressed recombinant MR and GR preferentially bound to the nGRE as a heterodimer, as identified in nuclear extracts of MR/GR-transfected COS-7 cells, and with higher affinity than MR or GR homodimers. In SN48 and COS-7 cells, concentration-dependent coactivation of MR and GR was required for maximal inhibitory action by corticosteroids and was abrogated in the L501P-GR mutant lacking DNA binding activity. Corticosteroid-mediated transcriptional inhibition was greater for MR/GR in combination than for MR or GR alone. These data represent the first identification of an nMRE/GRE and indicate that heterodimerization of MR and GR mediates direct corticosteroid-induced transrepression of the 5-HT1A receptor promoter.
 ...
PMID:Heterodimerization of mineralocorticoid and glucocorticoid receptors at a novel negative response element of the 5-HT1A receptor gene. 1127 86

Eight novel N-heteroarylalkyl-N-phenylpiperazines have been synthesized, chemically characterized and evaluated for in vitro binding affinity at the dopamine and serotonin receptors. Synaptosomal membranes of fresh bovine caudate nuclei (D1 and D2), the membranes of COS-7 cells (D4.4) and those prepared from fresh bovine hippocampi (5-HT1A) were used as a source of the corresponding receptor subtypes. [3H]SCH 23390 (D1-selective), [3H]spiperone (D2- and D4.4-selective) and [3H]-8-OH-DPAT (5-HT1A-selective) served as radioligands. None of the compounds expressed the affinity for the binding at the D1 subtype receptor. Compounds 7-9 containing a single methylene group serving as a bridge between heteroaryl- and N-phenylpiperazine part of the molecule were inactive [3H]spiperone and [3H]-8-OH-DPAT competitors. Ligands 15-19 (three methylene groups connecting heteroaryl- and N-phenylpiperazine part of the molecule) acted as moderate competitors of [3H]spiperone binding at the D2 receptor subtype, with the exception of 15 (a thione) which expressed a high binding affinity at the D2 receptor subtype. Compounds 15-19 behaved as moderate displacers of 8-OH-[3H]DPAT. Among all eight novel ligands only compound 15 expressed a moderate binding affinity at the D4.4 receptor subtype.
 ...
PMID:Investigation of mixed D2/5-HT1A activity of N-heteroarylmethyl-N-phenylpiperazines, N-heteroarylethyl-N-phenylpiperazines and N-heteroarylpropyl-N-phenylpiperazines. 1168 28


<< Previous 1 2