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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NIH-3T3 fibroblasts have been transfected with human serotonin 5-HT1A receptors. Clonal cell lines expressed between 40 and 500 fmol receptor/mg. 5-HT1A agonists strongly inhibited nonstimulated- as well as forskolin- or isoproterenol-stimulated adenylyl cyclase. The effects of 5-HT1A receptor activation on cell growth were investigated. 5-HT1A agonists accelerated cell division, generated foci, and increased DNA synthesis. The stimulation of [3H]thymidine incorporation was much stronger when tyrosine kinase receptors were activated concomitantly. Cyclic AMP (cAMP) elevating agents inhibited DNA synthesis induced by all mitogens tested. The mitogenic activity of 5-HT1A agonists did not seem to be linked to adenylyl cyclase inhibition because 1) we were not able to measure any decrease in intracellular cAMP levels under the conditions of DNA synthesis assay and 2) 2',5'-dideoxyadenosine, which strongly inhibited adenylyl cyclase, was not mitogenic and did not modify the mitogenic effects of 5-HT1A agonists. Pertussis toxin completely blocked potentiation of epidermal growth factor effect induced by 8-hydroxy-di-(n-propyl)aminotetralin, a 5-HT1A agonist, but only partially blocked the one induced by insulin. In conclusion, in transfected NIH-3T3 cells, transforming and mitogenic effects of 5-HT1A agonists involve a pertussis toxin-sensitive G protein but do not seem to be linked to adenylyl cyclase inhibition.
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PMID:Activation of 5-HT1A receptors expressed in NIH-3T3 cells induces focus formation and potentiates EGF effect on DNA synthesis. 133 92

To determine whether a cloned receptor coupled to pertussis toxin (PTx)-sensitive G-proteins can induce cell proliferation and oncogenic transformation, as observed for receptors that elicit PTx-insensitive enhancement of phosphatidyl inositol (PI)-specific phospholipase-C (PLC) activity, nontransformed murine BALB/c-3T3 cells were transfected with the rat serotonin-1A (5-HT1A) receptor. The 5-HT1A receptor is coupled to PTx-sensitive G-proteins to induce a cell-specific activation of PLC. While 1 microM 5-HT induced no change in PI turnover or cytosolic free calcium levels ([Ca2+]i) in receptor-negative nontransfected 3T3 cells, 5-HT induced a 2-fold increase in inositol trisphosphate accumulation and a 2.5-fold increase in [Ca2+]i in the 3T3-ZD8 clone, which expressed 0.6 +/- 0.2 pmol/mg protein of specific 5-HT1A binding sites. The stimulatory actions of 5-HT on PI turnover and [Ca2+]i in 3T3ZD8 cells displayed the pharmacology of the 5-HT1A receptor and were abolished by pretreatment with PTx. Thus, BALB/c-3T3 fibroblast cells express the PLC-linked pathway of the 5-HT1A receptor. Overnight treatment with 5-HT (1 microM) enhanced incorporation of [3H]thymidine into DNA extracted from serum-starved 3T3ZD-8 cells, an action that was also blocked by pretreatment with pertussis toxin. Long term (1-2 weeks) exposure to 5-HT in the medium led to phenotypic transformation of the cells, including the formation of foci with 1 microM 5-HT. These actions of 5-HT were not observed in untransformed 3T3 cells. We conclude that the PTx-sensitive PLC-linked pathway of the 5-HT1A receptor expressed in nontransformed BALB/c-3T3 cells, in concert with other serum-derived factors, predisposes the cells to enhanced proliferation and transformation.
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PMID:Conditional transformation mediated via a pertussis toxin-sensitive receptor signalling pathway. 160 83

We report the cloning and expression of a novel 5-HT receptor gene from human genomic DNA. This clone, HGCR1, contains an apparently intronless open reading frame of 390 amino acids with the seven hydrophobic regions, typical of G-protein coupled receptors. The deduced amino acid sequence of HGCR1 is 39%, 55% and 87% identical to that for the human 5-HT1A, the human 5-HT1D and the rat 5-HT1B receptor, respectively. [3H]5-HT binding to transfected COS-7 cell membranes yields a pharmacological profile similar to that of 5-HT1B receptor. Thus these findings indicate the presence of 5-HT1B-type receptor in the human.
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PMID:Cloning and expression of the human 5-HT1B-type receptor gene. 161 Mar 47

Regulation of phosphate uptake was studied in a HeLa cell line after transfection with DNA encoding the human 5-HT1A receptor. In these cells, 5-HT stimulates sodium-dependent phosphate uptake via protein kinase C activation. Endogenous histamine H1 receptors (739 +/- 20 fmol/mg protein) were identified with [3H]pyrilamine. Histamine (i) stimulated phosphoinositide hydrolysis (EC50 = 8.6 +/- 4.1 microM), (ii) activated protein kinase C (2.4-fold increase in activity), and (iii) increased phosphate uptake (EC50 = 3.2 +/- 1.8 microM) by increasing maximal transport (Vmax(basal) = 6.2 +/- 0.3 versus Vmax(histamine) = 9.1 +/- 0.4) without changing the affinity of the transport process for phosphate. Prolonged treatment with 16 microM phorbol 12-myristate 13-acetate completely blocked protein kinase C activation and markedly attenuated the stimulation of phosphate uptake induced by histamine, establishing that 5-HT and histamine stimulate phosphate uptake through the common pathway of protein kinase C activation. The linkages of the histamine H1 and 5-HT1A receptors to G protein pools were assessed in two ways. (i) The stimulation of phosphoinositide hydrolysis, protein kinase C activity, and phosphate uptake associated with histamine were insensitive to pertussis toxin, whereas those associated with 5-HT were very sensitive to pertussis toxin. (ii) The stimulation of phosphoinositide hydrolysis, protein kinase C activity, and phosphate uptake induced by histamine and 5-HT were additive. These findings suggest that distinct receptor types can stimulate phosphoinositide hydrolysis, protein kinase C, and phosphate uptake in an additive fashion through distinct pools of G proteins in a single cell type.
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PMID:5-HT1A and histamine H1 receptors in HeLa cells stimulate phosphoinositide hydrolysis and phosphate uptake via distinct G protein pools. 184 68

Most of the known neurotransmitters interact with more than one type of receptor. Some of them even dispose of receptor subtypes to exert their actions. Serotonin, far from being an exception to that, possesses at least 3 classes of receptors, which have all been reported to be heterogeneous, although convincing data only exist for the 5-HT1 class. This name has been proposed in 1979, two years before the introduction of 'A' and 'B' in the nomenclature to account for the observed heterogeneity of these sites. The 5-HT1C receptor subtype was first described in 1984 and the last member of the family, named 5-HT1D, was characterized in 1987. The pharmacological profiles, the signal transducing systems and the anatomical localizations, both at the regional and cellular levels, of all these subtypes have been investigated and possible functions have been proposed for each of them. Moreover, last and most definitive demonstration of the subtype individuality, the gene or complementary DNA coding for the 5-HT1A and 5-HT1C (and 5-HT2) receptors have been cloned and sequenced. Such data are still missing for 5-HT1D (and 5-HT1B) receptors, but will certainly be provided in the next few years. However and waiting for this decisive clue, the characterization of the 5-HT1D subtype leaves no doubt concerning its significance as a function 5-HT receptor. This review will concentrate on the characteristics of this subtype of 5-HT receptor.
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PMID:The serotonin 5-HT1D receptor: a progress review. 221 49

Using a probe derived from the human 5-HT1A receptor gene (G-21), a strongly hybridizable clone was identified from a rat genomic DNA library. This clone (G21Y2) had an overall deduced amino acid sequence that was 88% homologous with that of the human 5-HT1A receptor. There was only an 18% and 19% amino acid homology with the rat 5-HT1C and 5-HT2 receptors, respectively. The G21Y2 appears to be an excellent candidate for the rat 5-HT1A receptor gene. As this manuscript was being prepared a report by Albert et al. (13) was published in which a probe to the hamster beta 2-adrenergic receptor was used to identify a rat genomic (Clone D) that demonstrated a sequence that was similar to G21Y2.
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PMID:The cloning and sequence analysis of the rat serotonin-1A receptor gene. 227 37

Regulation of phosphate uptake was studied in HeLa cell lines after transfection with DNA encoding the human 5-HT1A receptor. Phosphate uptake was saturable and greater than 90% sodium-dependent, with Vmax approximately 30-35% without changing Km. Treatment with 5-HT or the 5-HT1A-specific agonist 8-OH-2-(di-n-propylamino)1,2,3,4-tetrahydronaphthalene increased Vmax approximately 40% without affecting Km. This effect was blocked by pretreatment with the 5-HT1 antagonists, methiothepine and spiperone, or pertussis toxin. Surprisingly, the stimulation was not secondary to an inhibition of adenylyl cyclase because 5-HT stimulated phosphate uptake approximately 20% in the presence of 1 mM 8-Br-cAMP. Rather, the primary pathway linked to the stimulation of phosphate uptake involved activation of protein kinase C because (i) 5-HT measurably activated protein kinase C in these cells, (ii) activators of protein kinase C (phorbol esters and diacylglycerol analogues) stimulated phosphate uptake in these cells (iii) the half-maximal doses for 5-HT-induced phosphatidylinositol hydrolysis and stimulation of phosphate uptake were virtually equivalent, and both effects were equally sensitive to pertussis toxin, and (iv) the stimulation was markedly attenuated in cells made deficient in protein kinase C. These results demonstrate that the stimulation of phosphatidylinositol hydrolysis by the 5-HT1A receptor can generate physiologically measurable effects on cellular transport and suggest that such accessory pathways may play a prominent role in signal transduction.
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PMID:The human 5-HT1A receptor expressed in HeLa cells stimulates sodium-dependent phosphate uptake via protein kinase C. 255 47

We studied the 5-HT1A receptor gene in 50 mood disorders and 50 normal volunteers. The 5-HT1A receptor gene was amplified by polymerase chain reaction and sequenced by the dideoxy method. The sequence of the 5-HT1A receptor encodes a protein of 422 amino acids, that is, one amino acid longer than the reported sequence (Kobilka et al. 1987). The DNA sequence at positions 454 to 459 is CGC GCC GCT, not CCG CGT, and the amino acids sequence at these positions is changing from proline arginine to arginine alanine alanine. These differences, however, were observed in both mood disorders and controls. One silent polymorphism, CTG to GTA at position 294, was found. These results suggest that the 5-HT1A receptor gene is intact in mood disorders.
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PMID:The gene encoding the 5-HT1A receptor is intact in mood disorders. 761 60

Serotonin is a well-known neurotransmitter and neuroimmunomodulator which has been reported to modulate T cell and NK cell proliferation. In this study we investigated whether serotonin could regulate mitogen-stimulated proliferation of the mature B lymphocyte. Mouse and rat spleen cells were cultured with serotonin in the presence or absence of a combination of Escherichia coli lipopolysaccharide and dextran sulfate, and proliferation was assessed by [3H]thymidine uptake or propidium iodide staining of DNA. Serotonin alone had no effect on spleen cell proliferation, while it increased mitogen-stimulated B cell proliferation in a dose- and time-dependent manner. These effects were reproduced by the selective 5-HT1A receptor agonist 8-OH-DPAT. Serotonin- or 8-OH-DPAT-induced increase in proliferation could be blocked by the 5-HT1A receptor antagonists (+)WAY 100135 and propranolol. Moreover, lipopolysaccharide-activated mouse spleen cells expressed specific binding sites for [3H]8-OH-DPAT. These results show that serotonin upregulates mitogen-stimulated B lymphocyte proliferation through 5-HT1A receptors, thus providing an important link between this neurotransmitter and the immune system.
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PMID:Serotonin upregulates mitogen-stimulated B lymphocyte proliferation through 5-HT1A receptors. 775 18

The author presents in her study the currently known serotonin effects on the immunity system, and the possibility of medicamentous utilization of agonists and antagonists of serotonin receptors in order to elucidate the effect of the 5-HT immunomodulating mechanism. 5-HT affects the antibody formation in sense of its reduction, the formation being evoked by antigenic stimuli. The mechanism involved however, is not entirely clear. The particular receptor being co-responsible in DNA synthesis inhibition is 5-TH1. The reduction of MHC-antigens expressiveness, which takes place due to serotonin, is intermediated by the classical 5-HT2 receptor. The procedure takes place in cooperation with 5-HT1A receptor. The serotonin induced augmented NK cells cytotoxicity is specifically mediated by 5-HT1 receptor. The participation of serotonin is assumed in pathogenesis of various diseases, there is however, relatively little knowledge about its effect on immunity system.
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PMID:[The role of serotonin in the regulation of the immune response]. 781 19


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