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 describe the nucleic acid sequence encoding a human 5-hydroxytryptamine1D (5-HT1D) serotonin receptor and some of the functional characteristics of the gene product. The receptor gene was isolated by hybridization to a probe based on a canine thyroid cDNA (called RDC4) previously isolated by others and believed to encode a heretofore undetermined member of the guanine nucleotide-binding protein (G protein)-linked receptor family. The human clone we isolated, called MA6A, contains an apparently intronless open reading frame encoding a 377-amino acid polypeptide with the seven hydrophobic domains characteristic of G protein-linked receptors. The MA6A deduced amino acid sequence is 88% identical to that for RDC4 and 43% identical to that for the human 5-HT1A receptor. Expression of the human gene product in transfected cell lines results in the appearance of saturable high affinity 5-HT1D-type [3H]5-HT binding. The expressed receptor exhibits features indicative of coupling to Gi proteins, i.e., robust inhibition of forskolin-stimulated cAMP accumulation and formation of a pertussis toxin-sensitive high agonist affinity binding state. These findings may help clarify several ambiguities in the classification and action of serotonin receptor subtypes.
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PMID:Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor. 165 50

The cDNA of RDC4, a putative receptor of the G protein-coupled receptor family, has been cloned by PCR methodology. The primary structure of this receptor showed homology with the serotonin 5-HT1A receptor. In this work, RDC4 mRNA has been injected in Y1 adrenal cells and Xenopus oocytes and RDC4 cDNA has been transfected transiently in cos-7 cells. In all these systems serotonin elicited a rise in cyclic AMP levels. Binding studies on membranes of the transfected cos-7 cells using [3H]-LSD showed a pattern of drug affinities consistent with the known properties of a 5-HT1D receptor. RDC4 therefore codes for a 5-HT1D receptor which in the studied systems is positively coupled to adenylate cyclase.
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PMID:The orphan receptor cDNA RDC4 encodes a 5-HT1D serotonin receptor. 165 18

RDC4 is a guanine nucleotide-binding protein-coupled receptor clone originally isolated from a canine thyroid cDNA library by Libert and colleagues [Science (Washington D. C.) 244:569-572 (1989)]. We have isolated the corresponding genomic clone for RDC4, have expressed this clone in murine LM (tk-) fibroblasts, and have determined that it encodes a serotonin 5-hydroxytryptamine1D (5-HT1D) receptor. RDC4 is an intronless gene encoding a protein of 377 amino acids, which exhibits greatest sequence identity (43%) to the 5-HT1A receptor and lower overall homology to other serotonergic and catecholaminergic receptors. Membranes prepared from murine LM (tk-) fibroblasts stably transfected with this clone were shown to bind [3H]5-HT in a saturable manner and displayed an apparently homogeneous population of high affinity (Kd = 3.6 nM, Bmax = 275 fmol/mg of protein) [3H]5-HT binding sites. High affinity [3H] 5-HT binding was unchanged using assay conditions [1 microM (+/- )-pindolol and 1 microM (R)-(+/- )-SCH 23390) to pharmacologically mask 5-HT1A, 5-HT1B, and 5-HT1C receptors. Serotonergic ligands displaced specific [3H]5-HT binding with a rank order of potency expected of a 5-HT1D receptor subtype, 5-carboxyamidotryptamine greater than 5-HT greater than yohimbine greater than 8-hydroxy-2-(di-n-propylamino)tetralin greater than ketanserin = spiperone greater than zacopride. Further, transfected cells responded to addition of 5-HT by decreasing the level of forskolin-stimulated cAMP accumulation. These data indicate that the gene RDC4 encodes a functional 5-HT1D receptor.
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PMID:Expression and pharmacological characterization of a canine 5-hydroxytryptamine1D receptor subtype. 175 39

1. [3H]-5-hydroxytryptamine (5-HT) has been shown to radiolabel at least five types of 5-HT binding sites in mammalian brain tissue, 5-HT1A, 5-HT1C, 5-HT1D and 5-HT1D and 5-HT1E (Frazer et al., 1990). Selective masking of 5-HT1A and 5-HT1C receptors, has uncovered binding sites which display both high (5-HT1D) and low (5-HT1E) affinity for 5-carboxamidotryptamine (5-CT). By utilizing [3H]-5-CT we have eliminated a portion of the complex binding (5-HT1E) seen when [3H]-5-HT is used as a radioligand. 2. [3H]-5-CT binding to 5-HT1D sites in bovine substantia nigra was rapid, reversible and saturable, displaying high affinity (Kd = 0.38 +/- 0.04 nM) and low non-specific binding (> 90% specific binding). 3. In bovine substantia nigra, [3H]-5-CT labelled an equivalent number of binding sites to [3H]-5-CT (403 +/- 18 and 362 +/- 20 fmol mg-1 protein, respectively) and binding was sensitive to guanine nucleotides. 4. A linear correlation (r2 = 0.99) existed between the potency of compounds to displace [3H]-5-HT and [3H]-5-CT in bovine substantia nigra. 5. Therefore, [3H]-5-CT is a novel radioligand for the examination of 5-HT1-like binding sites, which under proper experimental conditions can be used to radiolabel selectively 5-HT-1D-like binding sites.
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PMID:[3H]-5-carboxamidotryptamine labels 5-HT1D binding sites in bovine substantia nigra. 840 31