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

We previously reported a significant mitogenic effect of serotonin (5-hydroxytryptamine, 5-HT) on human small-cell lung carcinoma cells (SCLC, GLC-8), mediated by both 5-HT1D and 5-HT1A receptors. Here we investigate possible interactions between the two receptor subtypes. Dose-effect curves obtained by simultaneously applying equipotent concentrations of the selective 5-HT1A agonist 8-OH-DPAT and the selective 5-HT1D receptor agonist sumatriptan are shifted to the right, although maximal effects are additive. The nonselective 5-HT antagonist metergoline displays higher potency when both receptor subtypes are activated. The 5-HT1D receptor antagonist GR127935 is markedly more potent against sumatriptan than against the sensitive portion of 5-HT effect. Indeed, both GR127935 and the 5-HT1A antagonist spiperone shift the EC50 for the residual effect of 5-HT from approximately 300 to 120-150 nM, suggesting that blocking one receptor subtype may facilitate activation of the other. Preincubation with either 8-OH-DPAT or sumatriptan suppresses the mitogenic response to the other specific receptor agonist; suppression is complete within 10 min at 37 degrees C, and is not observed when the preincubation is done at 4 degrees C. Measurements of adenylate cyclase activity do not help in interpreting the results. Conversely, measurements of MAP kinase activity reveals biphasic activation with a delayed activation at 1 h, and reproduce the suppression of the effect of the second drug by 15 min preincubation. These findings constitute the first evidence of a reciprocal negative interference between human 5-HT1A and 5-HT1D receptors, and indicate that SCLC GLC-8 cells simultaneously express both receptor subtypes. Mere reciprocal antagonism of the drugs employed cannot account for these data. We suggest that in this cell system cross-talk occurs in the transduction pathways of the two receptor subtypes.
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PMID:Evidence for receptor subtype cross-talk in the mitogenic action of serotonin on human small-cell lung carcinoma cells. 901 44

In the present work, we tested the hypothesis that serotonin (5-hydroxytryptamine = 5-HT) might activate the extracellular signal-regulated kinase (ERK) pathway in human peripheral blood mononuclear cells (PBMC). PBMC were maintained in culture for 72 hrs at 37 degrees C prior to the addition of 5-HT. Our results showed an increase in ERK activation by 5-HT with a peak effect at 30 min and maximal stimulation with 5-HT at 1microM. This activation of ERK did not occur in adherent monocytes suggesting that the effect was on lymphocytes. In addition, p38 MAP kinase was not activated under these conditions. The effect of 5-HT on ERK activation appeared to be mediated through the activation of 5-HT1A receptors since similar results were obtained with R-+-8-hydroxy-DPAT, a selective 5-HT1A receptor agonist and WAY100635, a selective 5-HT1A receptor antagonist, reversed the 5-HT and the R-+-8-hydroxy-DPAT effects. Results from Western blot analysis confirmed the presence of 5-HT1A receptors on the PBMC. A 5-HT2A antagonist, ketanserin, and a 5-HT transport inhibitor, fluoxetine, both failed to block the activation of ERK by 5-HT. Our results indicate that 5-HT activates ERK, but not p38, MAP kinase of human PBMC via a 5-HT1A receptor.
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PMID:5-HT activates ERK MAP kinase in cultured-human peripheral blood mononuclear cells via 5-HT1A receptors. 1553 May 5

Neurotrophic growth factors are involved in cell survival. However, natural growth factors have a very limited therapeutic use because of their short half-life. In the present study, we investigated the mechanism of action of a non-peptidic neurotrophic drug, Xaliproden, a potential molecule for the treatment of motoneuron diseases, since the transduction pathways of this synthetic 5-HT1A agonist are very poorly understood. Xaliproden does not activate the Trk receptor but causes a rapid increase in the activities of the ERK1 and ERK2 isoforms of MAP kinase, which then rapidly decrease to the basal level. We demonstrate that isoforms of the SHC adapter protein are phosphorylated independently of each other and are probably not the source of the Xaliproden-induced MAP kinases activation. The inhibitor of Ras farnesylation, FPT-1, and the protein kinase C inhibitors, GF 109203X and chelerythrine, inhibited the Xaliproden-induced MAP kinase activation, suggesting p21Ras and PKC involvement. Moreover, the observations that the 5-HT1A antagonist, pindobind, and pertussis toxin abolished the Xaliproden-induced ERK stimulation suggested that Xaliproden activates the MAP kinase pathways by stimulating the G protein-coupled receptor, 5-HT1A. These results demonstrate clearly that the non-peptidic compound, Xaliproden, exerts its neurotrophic effects through a mechanism of action differing from that of neurotrophins. These findings suggest that this compound does not involve MAPK activation by TrkA receptor stimulation but acts by MAP kinase pathway by a pertussis toxin-sensitive mechanism involving 5-HT1A receptors, p21 Ras and MEK-1 and by PKC and Akt pathways.
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PMID:Xaliproden (SR57746A) induces 5-HT1A receptor-mediated MAP kinase activation in PC12 cells. 1588 46

Brain serotonin 1A (5-HT1A) receptors play an important role in mood disorders and can modulate various intracellular signaling mechanisms. We previously reported that systemic administration of either full or partial 5-HT1A agonists increases neuroendocrine responses and that tandospirone, an azapirone partial agonist, can activate (phosphorylate) extracellular signal-regulated kinase (ERK) in the hypothalamic paraventricular nucleus (PVN). In contrast, decreased levels of phosphoERK (pERK) have been reported in hippocampus following in vivo administration of either azapirone or aminotetralin 5-HT1A agonists, such as 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT). The present study investigated the time-dependent activation of MAP kinase in hypothalamus by (+)8-OH-DPAT to determine the regional differences and receptor specificity of the changes in pERK. Adult male rats received a systemic injection of (+)8-OH-DPAT (200 microg/kg, s.c.). The time-dependent changes in ERK activation were examined in hypothalamic nuclei as well as other brain regions associated with modulation of mood. (+)8-OH-DPAT produced a rapid increase (at 5 min) and transient return (at 15 min) of pERK levels in PVN and medial basal hypothalamus. In contrast, pERK levels in hippocampus were reduced at both 5 and 15 min after (+)8-OH-DPAT. Pretreatment with the 5-HT1A receptor-specific antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY100635) completely blocked the (+)8-OH-DPAT-mediated changes in pERK levels in PVN, medial basal hypothalamus, and hippocampus. No significant (+)8-OH-DPAT-induced changes in pERK were observed in dorsal raphe or amygdala. In conclusion, these results demonstrate that 8-OH-DPAT activation of MAP kinase signaling in vivo is a transient and region-specific phenomenon and in rat hypothalamus and hippocampus is mediated by 5-HT1A receptors.
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PMID:5-HT1A receptors mediate (+)8-OH-DPAT-stimulation of extracellular signal-regulated kinase (MAP kinase) in vivo in rat hypothalamus: time dependence and regional differences. 1797 47