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R Weinshank

Publications and source records attributed to R Weinshank.

6 recordsLinked to original sources
PubMed1997

Distribution of the neuropeptide Y Y2 receptor mRNA in rat central nervous system.

Our group has recently reported the expression cloning of the human neuropeptide Y Y2 receptor DNA and subsequently the cloning of the rat homologue. These studies have made it possible to localize the mRNA encoding this NPY receptor subtype in rat tissues. We have, thus, carried out in situ hybridization studies, using radiolabeled oligonucleotide probes to the rat Y2 receptor mRNA, to determine the distribution of Y2 mRNA in rat brain and limited peripheral ganglia. Probe specificity was confirmed by testing antisense and sense probes in transfected cells. In rat brain, hybridization signals obtained with the antisense probes were discrete and were restricted to neuronal profiles in specific subregions of the cortex, hippocampus, amygdala, thalamus, hypothalamus, mesencephalon and pons. Among the regions exhibiting the most intense labeling were the CA3 region of the hippocampus, the arcuate nucleus of the hypothalamus and layer 3 of the piriform cortex. Other regions containing labeled neurons included the medial amygdala, the centromedial thalamic nucleus, the dorsal raphe, the dorsal motor nucleus of the vagus and the trigeminal ganglion. The present results indicate that the mRNA encoding the Y2 receptor is discretely localized in the rat brain and that the distribution is generally consistent with previous radioligand-binding studies. This study should help clarify the relationship between the Y2 receptor distribution and functional studies of NPY receptor subtype classification and provides further evidence for the involvement of the Y2 receptor in multiple physiological processes.

Animals↗
PubMed1996

[3H]5-hydroxytryptamine labels the agonist high affinity state of the cloned rat 5-HT4 receptor.

We have used the cloned rat 5-HT4 receptor, and determined that the single protein product produced is able to bind both [3H]5-HT and [3H]GR113808 ([1-[(2-methyl sulphonyl) amino] ethyl-4-piperidinyl] methyl-1-methyl-1H-indole-3-carboxylate) with high affinity. The affinities of agonists for the [3H]5-HT (agonist)-labelled receptor were significantly higher than for the [3H]GR113808 (antagonist)-labelled receptor. Furthermore, [3H]5-HT binding was reduced by addition of guanyl nucleotides. These results strongly support the hypothesis that the 5-HT4 receptor displays two interconvertible affinity states (high and low) for agonists, characteristic of many G protein coupled receptors. [3H]5-HT, at the concentration employed, therefore labels the agonist high affinity state of the 5-HT4 receptor in systems in which high densities of this receptor are found.

Affinity Labels↗
PubMed1991

Human dopamine D5 receptor pseudogenes.

Molecular cloning studies have now identified five structurally homologous genes encoding the biosynthesis of the human dopamine receptors, DRD1, DRD2, DRD3, DRD4, and DRD5. Two of these dopamine receptors (DRD1 and DRD5) are encoded by intronless genes. To ascertain whether there are other intronless genes that share identity with the gene (DRD5) encoding the DRD5 receptor, we used a cloning method based on the polymerase chain reaction (PCR). Human genomic DNA was amplified by PCR with oligodeoxyribonucleotides (oligos) based on the DRD5 nucleotide (nt) sequence. Amplification of nt sequences between these oligos allowed the isolation of two independent intronless genes that share identity with DRD5. The full-length clones have also been isolated by screening human genomic libraries. The deduced amino acid sequences for these genes, PG-1 and PG-2, share 91% and 92% identity to DRD5, respectively. However, each of the genes contains differences in the coding regions that would render these genes incapable of encoding functional receptors. Thus, the human genome contains at least two DRD5 pseudogenes, consistent with in situ human chromosomal hybridization analysis which reveals the presence of two pseudogenes.

Amino Acid Sequence↗
PubMed1986

Structural heterogeneity and functional domains of murine immunoglobulin G Fc receptors.

Binding of antibodies to effector cells by way of receptors to their constant regions (Fc receptors) is central to the pathway that leads to clearance of antigens by the immune system. The structure and function of this important class of receptors on immune cells is addressed through the molecular characterization of Fc receptors (FcR) specific for the murine immunoglobulin G isotype. Structural diversity is encoded by two genes that by alternative splicing result in expression of molecules with highly conserved extracellular domains and different transmembrane and intracytoplasmic domains. The proteins encoded by these genes are members of the immunoglobulin supergene family, most homologous to the major histocompatibility complex molecule E beta. Functional reconstitution of ligand binding by transfection of individual FcR genes demonstrates that the requirements for ligand binding are encoded in a single gene. These studies demonstrate the molecular basis for the functional heterogeneity of FcR's, accounting for the possible transduction of different signals in response to a single ligand.

Amino Acid Sequence↗
PubMedDate not supplied

The molecular biology of serotonin receptors. An overview.

Recently, the family of G protein-coupled serotonin (5-hydroxytryptamine[5-HT]) receptors has begun to yield to molecular analysis. The cloning of the 5-HT1C and 5-HT2 receptors has provided a structural basis for the similarities observed in their pharmacologic properties. Furthermore, pharmacologic characterization of the transfected human 5-HT2 receptor has answered two outstanding questions regarding this receptor. First, the few amino acid differences that exist between the human and the rat genes are sufficient to account for the species differences seen in their pharmacologic properties. Second, the single protein encoded by the human 5-HT2 receptor gene is capable of binding both [3H]DOB and [3H]ketanserin. Analysis of the effects of guanine nucleotides provides further evidence that this single protein binds both ligands, that this receptor has high- and low-affinity states, and that these states are partially interconvertible. Furthermore, the close relationship between the adrenergic receptors and the 5-HT1A receptor has been reaffirmed by the recent cloning of a new adrenergic receptor subtype, alpha 2B, by use of the 5-HT1A receptor sequence. Finally, the detailed level of structural information now available on serotonin receptors has yielded valuable information about the ligand binding site and about the possible functional significance of differing rates of evolutionary change in various parts of the gene.

Animals↗