Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a case of a human gastric composite tumor occurring seven years after a partial gastrectomy for a low grade B cell MALT lymphoma. Histological examination of the tumor revealed two intimately intermingled components: 1. A moderately to poorly differentiated tubulo-acinar adenocarcinoma with signet-ring cells; and 2. Isolated or clustered small neuroendocrine cells without atypia expressing chromogranin A, somatostatin and/or glucagon, serotonin (5-HT) and, the 5-HT2B receptors. In addition to immunohistochemical detection, the presence of 5-HT2B receptors was shown pharmacologically through [125I]-DOI binding. Since 5-HT2B receptors have been demonstrated to have autocrine functions and, mitogenic and transforming properties, these results suggest a role of 5-HT in neuroendocrine malignant transformation. On the other hand, the expression of somatostatin and the detection by reverse transcriptase polymerase chain reaction (RT-PCR) of somatostatin receptor subtypes 2, 3, and 5, which have been shown to be involved in tumor regression, might account for the long evolution of this case (> 5 yr). This case illustrates the importance of local humoral modulation in tumor growth. Moreover, ultrastructural results favor a unique origin of the tumor cells from one amphicrine cell type.
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PMID:Histological, immunohistochemical, ultrastructural and biochemical study of human gastric composite tumor: expression of the serotonin-2B receptor by the neuroendocrine component. 1147 72

The occurrence of human cerebellar serotonin 5-HT(2A) receptors (5-HT(2A)R) is equivocal and their status in schizophrenia unknown. Using a range of techniques, we investigated cerebellar 5-HT(2A)R expression in 16 healthy subjects and 16 subjects with schizophrenia. Immunocytochemistry with a monoclonal antibody showed labelling of Purkinje cell bodies and dendrites, as well as putative astrocytes. Western blots showed a major band at approximately 45 kDa. Receptor autoradiography and homogenate binding with [(3)H]ketanserin revealed cerebellar 5-HT(2A)R binding sites present at levels approximately a third of that in prefrontal cortex. 5-HT(2A)R mRNA was detected by reverse transcriptase-polymerase chain reaction, with higher relative levels in men than women. Several aspects of 5-HT(2A)R expression were altered in schizophrenia. 5-HT(2A)R immunoreactivity in Purkinje cells was partially redistributed from soma to dendrites and was increased in white matter. 5-HT(2A)R mRNA was decreased in the male patients. 5-HT(2A)R measured by dot blots and [(3)H]ketanserin binding (B(max) and K(d)) were not significantly altered in schizophrenia. These data show that 5-HT(2A)R gene products (mRNA, protein, binding sites) are expressed in the human cerebellum at nonnegligible levels; this bears upon 5-HT(2A)R imaging studies which use the cerebellum as a reference region. 5-HT(2A)R expression is altered in schizophrenia; the shift of 5-HT(2A)R from soma to dendrites is noteworthy since atypical antipsychotics have the opposite effect. Finally, the results emphasise that expression of a receptor gene is a mutifaceted process. Measurement of multiple parameters is necessary to give a clear picture of the normal situation and to show the profile of alterations in a disease.
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PMID:Expression of serotonin 5-HT(2A) receptors in the human cerebellum and alterations in schizophrenia. 1157 47

Previous studies indicate expression of various serotonin receptor subtypes, including the 5-HT(1A) receptor subtype, in rodent cochlear nucleus. Our long-term goal is to identify the types of cochlear nucleus neurons, which are well described in cat, that express 5-HT receptors. In the current study, the reverse transcriptase/polymerase chain reaction and the in situ hybridization method were used to detect the mRNA encoding a portion of the 5-HT(1A) receptor subtype in the cochlear nucleus of the cat.
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PMID:5-HT(1A) receptor subtype mRNA expression in cochlear nucleus. 1195 May 27

The effects of 5-hydroxytriptamine (5-HT, serotonin) are mediated via five main receptor types of which the 5-HT7 receptor is the most recently characterised member. The 5-HT7 receptor has been shown to participate in mediating cranial blood vessels dilatation that may result in migraine headache. We report here the cDNA cloning, sequencing and tissue distribution of porcine 5-HT7 receptor and illustrate its comparison with corresponding receptor of known species. Employing a combination of reverse transcriptase and inverse polymerase chain reaction we amplified and sequenced a full length cDNA from the porcine cerebral cortex. The deduced amino acid sequence comparison confirmed that the cloned porcine receptor belongs to 5-HT7 receptor as described for human and other species and showing overall homology of 92-96%. The expression of 5-HT7 receptor mRNA was observed in porcine central (cerebral cortex, trigeminal ganglion and cerebellum) as well as in peripheral (pulmonary and coronary arteries, superior vena cava and saphenous vein) tissues. The established cDNA sequence and tissue distribution of porcine 5-HT7 receptor will be helpful in exploring the role of this receptor in pathophysiological processes and to predict as a potential therapeutic target for antimigraine drug development.
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PMID:Molecular cloning and tissue distribution of mRNA encoding porcine 5-HT7 receptor and its comparison with the structure of other species. 1234 12

Serotonin [5-hydroxytryptamine (5-HT)]-mediated cardiac valvular disease has been commonly observed in patients with carcinoid tumors. Previous research by others using reverse transcriptase-polymerase chain reaction demonstrated that aortic valve cells expressed predominantly 5-HT(2A/2B) receptors (5-HT(2A)R). Related investigations by our group using sheep aortic valve interstitial cell (SAVIC) cultures demonstrated that 5-HT both up-regulates transforming growth factor (TGF)-beta1 expression and activity, and also results in increased phospholipase C (PLC) activity. Thus, the present study investigated the hypothesis that the 5-HT signaling pathway in SAVICs involves 5-HT(2)Rs with associated G-protein signal transduction. The objectives were to functionally characterize in SAVIC cultures the native serotonin receptor subtypes using specific agonists and antagonists, and to delineate the serotonin-signaling pathway. 5-HT administration caused a marked stimulation of PLC activity. SAVIC studies of specific agents that target the 5-HT(2)R subtypes indicate that this response seemed to be mediated predominantly by 5-HT(2A)Rs. Furthermore, the sheep 5-HT(2A)R was identified by reverse transcriptase-polymerase chain reaction with sequence confirmation including comparisons to pig and human 5-HT(2A)R. Extracellular signal-regulated kinase (Erk 1/2) is a signaling molecule downstream from the 5-HT(2A)R. Both a protein kinase C inhibitor, GF109203X, and a Src inhibitor, PP1, attenuated 5-HT-stimulated Erk 1/2 activation. However, a 5-HT(2A)R antagonist, MDL 100907, inhibited 5-HT up-regulation of PLC and TGF-beta1, while having far less pronounced effects on Erk 1/2. In conclusion, these studies of the signal transduction activity of SAVICs in response to 5-HT have demonstrated that the 5-HT(2A)Rs are the most functionally active of the 5-HT(2)Rs in this cell type. Furthermore, 5-HT(2A)Rs are also involved in 5-HT up-regulation of active TGF-beta. 5-HT also mediated strong Erk 1/2 signaling via the MAP-kinase pathway, which was only in part because of 5-HT(2A)R activity. Thus, major 5-HT Erk 1/2 signaling beyond that controlled by 5-HT(2)Rs must involve other serotonin receptor types and/or secondary signaling events.
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PMID:Serotonin mechanisms in heart valve disease II: the 5-HT2 receptor and its signaling pathway in aortic valve interstitial cells. 1246 35

Serotonin 5-HT(7) receptors are present in astrocytes. Understanding their role in this type of cell would greatly benefit from the identification of astroglial cell lines expressing this receptor type. The aim of the present study was to assess the expression of native 5-HT(7) receptors and 5-HT(7) receptor mRNA in a number of human glioblastoma cell lines, by means of cAMP measurements, Western blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. 5-Hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT), 5-methoxytryptamine (5-MeOT) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) induced concentration-dependent stimulations of cAMP accumulation in the human glioblastoma cell lines, U-373 MG, U-138 MG, U-87 MG, DBTRG-05MG, T98G, H4, CCF-STTG1 and Hs 683. The rank order of potency was 5-CT>5-HT=5-MeOT>>8-OH-DPAT. The effect of 5-CT was inhibited in a concentration-dependent manner by the selective 5-HT(7) receptor antagonist SB-269970 in all human glioblastoma cells. Schild analyses yielded slope factors close to unity (0.89-1.13) and pA(2) values of 8.69-9.05. Western blot analysis revealed the presence of immunoreactive bands corresponding to the human 5-HT(7) receptor in extracts of all human glioblastoma cell lines. The presence of the three splice variants of the 5-HT(7) receptor (5-HT(7(a/b/d))) was visualized by RT-PCR analysis with specific primers in all human glioblastoma cell lines. In conclusion, human glioblastoma cell lines express functional 5-HT(7) receptors and the three splice variants of the corresponding mRNA. These cell lines could serve as model systems of native 5-HT(7) receptors in glial cells to investigate their putative role in processes like release of neurotrophic factors or inflammatory cytokines.
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PMID:Functional expression of the serotonin 5-HT7 receptor in human glioblastoma cell lines. 1533 60

The role of interneurons in neurovascular coupling was investigated by patch-clamp recordings in acute rat cortical slices, followed by single-cell reverse transcriptase-multiplex PCR (RT-mPCR) and confocal observation of biocytin-filled neurons, laminin-stained microvessels, and immunodetection of their afferents by vasoactive subcortical cholinergic (ACh) and serotonergic (5-HT) pathways. The evoked firing of single interneurons in whole-cell recordings was sufficient to either dilate or constrict neighboring microvessels. Identification of vasomotor interneurons by single-cell RT-mPCR revealed expression of vasoactive intestinal peptide (VIP) or nitric oxide synthase (NOS) in interneurons inducing dilatation and somatostatin (SOM) in those eliciting contraction. Constrictions appeared spatially restricted, maximal at the level of neurite apposition, and were associated with contraction of surrounding smooth muscle cells, providing the first evidence for neural regulation of vascular sphincters. Direct perfusion of VIP and NO donor onto the slices dilated microvessels, whereas neuropeptide Y (NPY) and SOM induced vasoconstriction. RT-PCR analyses revealed expression of specific subtypes of neuropeptide receptors in smooth muscle cells from intracortical microvessels, compatible with the vasomotor responses they elicited. By triple and quadruple immunofluorescence, the identified vasomotor interneurons established contacts with local microvessels and received, albeit to a different extent depending on interneuron subtypes, somatic and dendritic afferents from ACh and 5-HT pathways. Our results demonstrate the ability of specific subsets of cortical GABA interneurons to transmute neuronal signals into vascular responses and further suggest that they could act as local integrators of neurovascular coupling for subcortical vasoactive pathways.
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PMID:Cortical GABA interneurons in neurovascular coupling: relays for subcortical vasoactive pathways. 1548 13

The serotonin 5-HT4 receptor (where 5-HT stands for 5-hydroxy-tryptamine) is a member of the seven transmembrane-spanning G-protein-coupled family of receptors and mediates many cellular functions both in the central nervous system and at the periphery. In the present study, we isolated and characterized the 5'-flanking region of the h5-HT4 (human 5-HT4) receptor. We demonstrate the existence of a novel exon that corresponds to the 5'-untranslated region of the h5-HT4 receptor gene. RNase protection analysis and reverse transcriptase-PCR experiments performed on human atrial RNA demonstrated that the major transcription start site of the h5-HT4 receptor gene is located at -3185 bp relative to the first ATG codon. In addition, a 1.2 kb promoter fragment which drives the transcription of the 5-HT4 receptor was characterized. The promoter region lacks TATA and CAAT canonical motifs in the appropriate location, but contains putative binding sites for several transcription factors. Transient transfection assays revealed that the (-3299/-3050) gene fragment possesses the ability to promote the expression of the luciferase reporter gene in human cell lines. In contrast, the promoter was silent in monkey COS-7 cells, indicating the requirement of specific factors to initiate transcription in human cells. In addition to the promoter element, enhancer activity was found in a region (-220/-61) located in the long 5'-untranslated region. Mutational analysis, gel shift and transfection assays identified an Nkx2.5 (NK2-transcription-factor-related 5)-like binding site as a regulatory sequence of this enhancer. Our results suggest a complex regulation of the h5-HT4 receptor gene expression involving distinct promoters and non-coding exons.
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PMID:Functional studies of the 5'-untranslated region of human 5-HT4 receptor mRNA. 1557 21

We report the cloning, molecular characterization, and pharmacological characterization of the canine 5-HT2A and 5-HT2B receptors. The canine and human 5-HT2A receptors share 93% amino acid homology. The canine and human 5-HT2B receptors are also highly conserved (87% homology) with the exception of the carboxyl termini where the canine protein is 62 amino acids shorter. Both the canine 5-HT2A and 5-HT2B receptors have high affinity for [3H]5-HT (KD=4.50+/-0.89 nM and 3.10+/-0.82 nM, respectively) and, in general, the pharmacology of these two receptors matches closely the pharmacology of their human homologs for the 19 serotonergic ligands tested. However, the functional response (Ca2+ mobilization) of the canine 5-HT2B receptor to several agonists was weaker compared to the human 5-HT2B receptor. Using quantitative reverse transcriptase polymerase chain reaction, a high expression level of canine 5-HT2A receptor mRNA was detected in the brain and lower levels in peripheral tissues, whereas the highest levels of canine 5-HT2B receptor mRNA were observed in lungs and smooth muscles. A significant level of canine 5-HT2B receptor mRNA was detected in brain tissue. The availability of the full sequence and pharmacology of the canine 5-HT2A and canine 5-HT2B receptors provides useful information for the interpretation of previous and future pharmacological studies of 5-HT2A/2B ligands in dog.
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PMID:Molecular and pharmacological characterization of serotonin 5-HT2A and 5-HT2B receptor subtypes in dog. 1586

Brain serotonin 5-HT(7) receptors are known to be expressed in neurons and astrocytes. We now report the presence of these receptors in a third type of cell, microglial cells. 5-Hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT), 5-methoxytryptamine (5-MeOT) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) induced concentration-dependent stimulations of cAMP accumulation in the human microglial MC-3 cell line. The maximal effect of 5-HT was 3.4+/-0.3-fold stimulation (mean+/-S.E.M., n=5) above basal levels. The rank order of agonist potency (pEC50 values) was 5-CT (7.09)>5-HT (6.13)>or=5-MeOT (5.78)>>8-OH-DPAT (ca. 5). The effect of 5-CT was inhibited in a concentration-dependent manner by the selective 5-HT7 receptor antagonist SB-269970 (pA2 value 9.03). Western blot analysis revealed the presence of immunoreactive bands corresponding to the human 5-HT7 receptor in extracts of MC-3 cells. The presence of two splice variants of the 5-HT7 receptor (5-HT7(a/b)) was visualized by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis with specific primers. In real-time PCR studies, the mRNA for interleukin-6 (IL-6) was found to be increased by 2.5-fold in MC-3 cells after 1 h incubation with 5-CT (1 microM) and this effect was fully blocked by the 5-HT7 receptor antagonist SB-269970 (1 microM). These data show that functional 5-HT7 receptors are present in human microglial MC-3 cells, suggesting that they are involved in neuroinflammatory processes.
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PMID:Serotonin 5-HT7 receptors coupled to induction of interleukin-6 in human microglial MC-3 cells. 1599 79


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