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)

Neuroendocrine (NE) differentiation within the primary prostate tumor has been correlated with tumor progression and shortened patient survival. Serotonin (5-hydroxytryptamine, 5-HT), a known mitogen, is found in most neuroendocrine cells of the human prostate. We have previously found that human prostatic carcinoma cell lines, PC-3, DU-145 and LNCaP, display certain NE characteristics. In this study, we have examined the effects of several subtype-selective 5-HT receptor antagonists on the growth of the three lines. Of these, the 5-HT1A antagonist pindobind had the most marked antiproliferative effect in vitro. Pindobind also had marked growth-inhibitory effects on the aggressive PC-3 cell line in vivo, in athymic nude mice. Radioligand binding studies indicated the presence of 5-HT binding sites on all three cell lines. Our results suggest that 5-HT is involved in the growth of prostate tumor cells and may serve as a target for treatment.
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PMID:Growth inhibition of human prostatic carcinoma cell lines by serotonin antagonists. 807 75

The functional activity and selectivity of the novel 5-HT1D receptor antagonist GR 127,935 (2'-methyl-4'(5-methyl-1,2,4 oxadiazol-3-yl)-biphenyl-4-carboxylic acid [4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide) was investigated at cloned human 5-HT1A, 5-HT1D alpha, 5-HT1D beta and opossum kidney (OK) 5-HT1B receptor sites. 5-HT1 receptor-mediated activity was studied by measuring the inhibition of forskolin-induced cAMP formation in cell lines expressing these receptors (Bmax (fmol/mg protein): human epitheloid carcinoma HeLa/5-HT1A: 1285, OK/5-HT1B: 52, Chinese hamster ovary CHO-K1/5-HT1D alpha: 181 and CHO-K1/5-HT1D beta: 685). GR 127,935 did not show 5-HT1D beta receptor-mediated agonist activity in permanently transfected CHO-K1 cells, whereas at submicromolar and higher concentrations intrinsic agonist activity was observed in HeLa/5-HT1A,OK/5-HT1B and CHO-K1/5-HT1D alpha cells. GR 127,935 showed potent (KB value: 1.3 nM) and silent antagonism at CHO-K1/5-HT1D beta receptor sites. The antagonist activity of 1 microM of GR 127,935 at CHO-K1/5-HT1D alpha and OK/5-HT1B receptor sites was only partial and less pronounced. This contrasts with the silent antagonism of methiothepin at the 5-HT1D alpha (KB value = 11.8 nM), 5-HT1D beta (KB value = 6.9 nM) and 5-HT1B (KB value = 49.3 nM) receptor subtypes. GR 127,935, when tested at 10 microM, was found to be a weak and partial antagonist of HeLa/5-HT1A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional effects of the 5-HT1D receptor antagonist GR 127,935 at human 5-HT1D alpha, 5-HT1D beta, 5-HT1A and opossum 5-HT1B receptors. 857 38

The growing relevance of prostate carcinoma in the developed world requires serious attention to focus on the risk-benefit relationships of the treatments used. Given the increasingly complex therapeutic approach to prostate carcinoma, an extensive range of knowledge is required. Androgen deprivation plays a central role in this disease. The management of androgen deprivation-derived toxicity in the form of hot flashes, metabolic syndrome, osteoporosis, cognitive disorders, etc., is of growing interest. The drug treatment of hot flashes involves hormone management that is not without oncological risk and moreover generates considerable toxicity. Antidepressants in turn play an important role in the non-hormone treatment of this disorder. Trazodone, a serotonin reuptake inhibitor/5-HT2A receptor antagonist affording more selective action upon the receptors implicated in hot flashes, could be of great interest. Trazodone shows great affinity for the 5-HT2A receptors and moderate affinity for the 5-HT1A receptors. Serotonin (5-hydroxytryptamine, or 5-HT) levels are known to be lowered in postmenopausal women, and normalize when replacement therapy is provided. This suggests that abrupt sexual hormone deprivation gives rise to a reduction in blood serotonin - with a subsequent increase in its hypothalamic 5-HT2A receptors. These receptors would be implicated in the physiopathology of hot flashes; as a result, the blocking of such receptors is one of the principal therapeutic measures. The use of trazodone, increasing the serotonin concentrations and blocking the 5-HT2A and 5-HT1A receptors, could be viewed as a novel management approach more in line with the physiopathology of hot flashes. Well designed comparative studies are needed to establish the efficacy of such treatment. Other issues pending clarification would be the most effective dose and duration of treatment for controlling hot flashes.
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PMID:[Trazodone: a new selective approach to the treatment of hot flashes induced by androgen deprivation in prostate carcinoma?]. 1971 46