X Zhao, B W McBride, L Trouten-Radford, K Lissemore
{"title":"Decreased insulin-like growth factor-I (IGF-I) receptor sites on circulating mononuclear cells from cows with persistent lymphocytosis.","authors":"X Zhao, B W McBride, L Trouten-Radford, K Lissemore","doi":"10.3109/10799899309063270","DOIUrl":"https://doi.org/10.3109/10799899309063270","url":null,"abstract":"<p><p>Plasma IGF-I concentrations and IGF-I receptor binding on mononuclear cells have been studied on bovine leukemia virus (BLV)-negative (CO), BLV-infected aleukemic (AL) cows or cows with persistent lymphocytosis (PL). No significant differences in plasma IGF-I concentrations were demonstrated among the three groups of animals. However, a linear negative correlation existed between the number of circulating mononuclear cells and the number of IGF-I binding sites on these cells from control cows. In addition, mononuclear cells from PL cows had fewer IGF-I binding sites per cell when compared with control cows. These results suggest involvement of IGF-I in etiology of BLV infection and progression and warrant further studies to establish whether IGF-I plays a major physiological role in these conditions.</p>","PeriodicalId":16948,"journal":{"name":"Journal of receptor research","volume":"13 8","pages":"1161-72"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799899309063270","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19242501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modelling by homology of the HSV1-TK sequence embedded structural alignment.","authors":"G Folkers, J Brünjes, M Michael, J Schill","doi":"10.3109/10799899309073652","DOIUrl":"https://doi.org/10.3109/10799899309073652","url":null,"abstract":"<p><p>Modelling by homology is an approach to the rational design of new drugs based on the construction of ligand protein interaction complexes. Because in most cases the 3D-structure of the target protein is not known from biophysical data, this approach yields a theoretical procedure which establishes at least parts of the protein by comparison with isofunctional proteins, assuming that much of the structural information is embedded in the amino acid sequence. This approach should be of considerable importance for proteins with divergent primary structures but with a high degree of isofunctionality, the latter demanding a similar active site folding pattern. This study is a pattern recognition approach based on additive secondary structure prediction and surface probabilities from residue variabilities. The comparison of the additive properties yields a sequence alignment of the viral thymidine kinases with the adenylate kinases having a closely related functionality. X-ray structures of adenylate kinases can then be used as templates to derive a 3D-structure prediction of the thymidine kinase active site.</p>","PeriodicalId":16948,"journal":{"name":"Journal of receptor research","volume":"13 1-4","pages":"147-62"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799899309073652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19368600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pseudo-receptor modeling: a new concept for the three-dimensional construction of receptor binding sites.","authors":"A Vedani, P Zbinden, J P Snyder","doi":"10.3109/10799899309073653","DOIUrl":"https://doi.org/10.3109/10799899309073653","url":null,"abstract":"<p><p>Molecular design of small molecules intended to target a macromolecule generally utilizes one of two computational approaches: \"receptor fitting\" or \"receptor mapping\". A comprehensive strategy for the design of potent, selective and novel ligands for cell-bound receptors combines the two by means of \"pseudoreceptor modeling\". Definition of a refined pharmacophore model is the first step. A subsequent step involves the construction of a pseudoreceptor--an explicit molecular binding pocket--for the bioactive conformation of a series of ligands with high affinity for a particular receptor subtype. The receptor-mapping program \"Yak\" allows the construction of a peptidic pseudoreceptor around any single small molecule or molecular ensemble of interest. The fidelity of the approach is exemplified by application to the active site of the enzymes human carbonic anhydrase I and thermolysin, followed by comparison with their known X-Ray crystal structures.</p>","PeriodicalId":16948,"journal":{"name":"Journal of receptor research","volume":"13 1-4","pages":"163-77"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799899309073653","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19368601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synthesis and biological properties of a biotinylated derivative of ACTH1-17 for MSH receptor studies.","authors":"C Bagutti, A N Eberle","doi":"10.3109/10799899309073657","DOIUrl":"https://doi.org/10.3109/10799899309073657","url":null,"abstract":"<p><p>A biotinylated derivative of [beta-Ala1,Lys17]-ACTH1-17-NH-(CH2)4-NH2 (ACTH1-17) was synthesized and biologically characterized. The heptadecapeptide with free N-terminus and blocked side-chains was prepared by the solid-phase method using TentaGel resin and a 4-aminobutylamide linker. Biotinyl-beta-Ala-OH was then coupled to the terminal amino group and the resulting [N alpha-(biotinyl-beta-alanyl)-beta-Ala1,Lys17]-ACTH1-17-NH-(CH2)4-N H2 (Bio-ACTH1-17) cleaved from the resin, purified and analyzed. Competition binding assays with mouse B16-F1 and human D10 and HBL melanoma cells using [125I]-alpha-MSH as radioligand gave dissociation constants for Bio-ACTH1-17 of 1.67 +/- 0.07 nM (B16-F1), 0.02 +/- 0.005 nM (D10) and 0.21 +/- 0.02 nM (HBL). The EC50 for Bio-ACTH1-17 in the B16 melanin assay was 4.15 +/- 1.0 nM. Analysis of the binding characteristics of [125I]-Bio-ACTH1-17 demonstrated that in human melanoma cells this radioligand was displaced by ACTH1-17 as well as alpha-MSH whereas in B16-F1 cells the tracer was only displaced from the binding site by ACTH1-17. Studies of Bio-ACTH1-17 with streptavidin showed that the peptide is to a large extent trapped specifically through reaction with biotin. These results demonstrate that (1) the biological characteristics of Bio-ACTH1-17 are almost identical to those of ACTH1-17, (2) Bio-ACTH1-17 is bound by avidin, and (3) Bio-ACTH1-17 may become a useful tool for MSH receptor targeting.</p>","PeriodicalId":16948,"journal":{"name":"Journal of receptor research","volume":"13 1-4","pages":"229-44"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799899309073657","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19368605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evidence for shared receptor proteins for human interleukin-3 and granulocyte-macrophage colony-stimulating factor in the human M-07 cell line.","authors":"G Woerly, G Zenke, U Strittmatter, B Ryffel","doi":"10.3109/10799899309073691","DOIUrl":"https://doi.org/10.3109/10799899309073691","url":null,"abstract":"<p><p>The biologic response of the human leukemia cell line M-07 to granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 3 (IL-3) and interleukin 4 (IL-4) is mediated by a low number of high affinity receptors. Cross-competition studies revealed that IL-3 and GM-CSF partially inhibited the specific binding of the heterologous radiolabeled ligand, whereas IL-4 binding was not affected by these cytokines. The molecular mechanism of cross-competition was investigated by chemical crosslinking and immunoprecipitation. Trimolecular receptor complexes consisting of a major 73kDa and two minor 120 and 128kDa membrane proteins for IL-3, and a major 84kDa and two minor 120 and 130 kDa proteins for GM-CSF were found on M-07 cells. The 73 and 84kDa proteins represent distinct and non-linked membrane proteins and are identical with the cloned, low affinity IL-3 and GM-CSF receptor proteins (Gearing et al, 1989, Hayashida et al, 1990). The higher molecular weight proteins share common binding sites as evidenced by immunoprecipitation of double-crosslinked membranes. The 120/128kDa proteins are most likely identical with the recently cloned and shared beta-subunit of the IL-3 and GM-CSF receptor (Kitamura et al, 1991) containing a single or two IL-3 and/or GM-CSF molecules.</p>","PeriodicalId":16948,"journal":{"name":"Journal of receptor research","volume":"13 1-4","pages":"753-75"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799899309073691","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19432900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Research and society: a relationship with two faces.","authors":"A Pletscher","doi":"10.3109/10799899309073641","DOIUrl":"https://doi.org/10.3109/10799899309073641","url":null,"abstract":"<p><p>Biomedical research has been and will continue to be essential for improving the quality of life but is also the origin of many of society's adverse reactions and problems. These are related to such issues as unfulfilled hopes, ethical considerations, potential misuse and financial constraints. They particularly endanger basic research and favour non-scientific-based practices in medicine. Future challenges for research include continuous improvement of its quality, conscientiousness, responsibility, communication with society and critical openness for unconventional approaches.</p>","PeriodicalId":16948,"journal":{"name":"Journal of receptor research","volume":"13 1-4","pages":"1-18"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799899309073641","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19433775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative analysis of beta-adrenergic receptor kinase and beta-arrestin mRNA expression in human cells.","authors":"G Parruti, G Ambrosini, M Sallese, A De Blasi","doi":"10.3109/10799899309073682","DOIUrl":"https://doi.org/10.3109/10799899309073682","url":null,"abstract":"<p><p>Receptor phosphorylation is a key step in the process of rapid desensitization. beta-Adrenergic receptor kinase is a specific receptor kinase that is known to phosphorylate and induce desensitization of several G-coupled synaptic receptors only when they are occupied by their agonists. We recently cloned human beta ARK cDNA and reported high levels of beta ARK expression in human peripheral blood leukocytes, also providing the first evidence for its possible functional role in these cells. Complete homologous receptor desensitization by beta ARK requires an additional cytosolic factor, called beta-arrestin. In the present study, we have cloned a 212 bp fragment of the human beta-arrestin cDNA to perform a comparative analysis of beta ARK and beta-arrestin mRNA expression in various human cell types. We found that also beta-arrestin mRNA is abundant in non-innervated tissues and cells. The fact that the entire machinery for G-coupled receptor desensitization is highly expressed in these cells further supports the idea that beta ARK may regulate nonsynaptic as well as synaptic receptors.</p>","PeriodicalId":16948,"journal":{"name":"Journal of receptor research","volume":"13 1-4","pages":"609-18"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799899309073682","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19434352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C Gotti, M Moretti, R Longhi, L Briscini, E Manera, F Clementi
{"title":"Anti-peptide specific antibodies for the characterization of different alpha subunits of alpha-bungarotoxin binding acetylcholine receptors present in chick optic lobe.","authors":"C Gotti, M Moretti, R Longhi, L Briscini, E Manera, F Clementi","doi":"10.3109/10799899309073672","DOIUrl":"https://doi.org/10.3109/10799899309073672","url":null,"abstract":"<p><p>Chick optic lobe express alpha-Bungarotoxin receptors. We have recently purified these receptors which, when reconstituted in a lipid bilayer, behave as functional acetylcholine gated channels. In order to characterize this purified preparation, we raised polyclonal antibodies against peptides obtained from the putative cytoplasmic domain between the hydrophobic sequence M3 and M4 of two previously cloned alpha-Bungarotoxin receptor subunits, alpha 7 and alpha 8. Both antibodies recognized the receptors present in the membrane extract and in the purified preparation, although the amount of the alpha-Bungarotoxin receptors precipitated by the two antibodies was quantitatively different. In Western blots of both purified and membrane-bound receptors, these antibodies specifically reacted with an M(r) 57000-55000 band. A study was also undertaken to quantify the receptors containing these subunits in different chick brain areas; it was found that the number of these subunits, as well as their ratio, was similar in all the tested areas. Furthermore, the alpha-Bungarotoxin receptors were present in at least two subtypes, one containing only the alpha 7 subunit and the other both alpha 7 and alpha 8 subunits.</p>","PeriodicalId":16948,"journal":{"name":"Journal of receptor research","volume":"13 1-4","pages":"453-65"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799899309073672","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19434380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chicken insulin discriminates between receptors for insulin and insulin-like growth factor I on centrally- and peripherally-derived glial cells.","authors":"F M Stanley","doi":"10.3109/10799899309063261","DOIUrl":"https://doi.org/10.3109/10799899309063261","url":null,"abstract":"<p><p>Insulin and IGF-I receptors in G26-20 cells, derived from a mouse oligodendroglioma, and in RN-2 cells, derived from a rat Schwannoma, were characterized by specific binding to [125I]insulin and [125I]IGF-I respectively. In both cell lines, the Kd for insulin was 1.5 nM. Insulin receptor number was 33,000/cell for RN-2 cells and 17,000 receptors/cell for G26-20 cells. RN-2 cells have 700,000 IGF-I receptors/cell with a Kd of 2 nM while G26-20 cells have 60,000 receptors/cell with an affinity of 4.9 nM. However, the independence of these two receptor populations in each cell type was equivocal since the subunit structure of these receptors appears identical by electrophoresis. In both cell lines, competition with insulin analogs for [125I]insulin binding demonstrated chicken insulin > insulin > IGF-I. Competition for [125I]IGF-I binding showed that IGF-I was approximately 85-fold more potent than insulin. Chicken insulin was ineffective at all concentrations. Thus, chicken insulin can be used as a specific ligand to unequivocally discriminate between IGF-I and insulin receptors and effects.</p>","PeriodicalId":16948,"journal":{"name":"Journal of receptor research","volume":"13 7","pages":"1009-30"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799899309063261","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19351610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Determination of the response of melanoma cells to melanocyte stimulating hormone by 31P nuclear magnetic resonance spectroscopy.","authors":"H Degani, J O DeJordy, Y Salomon","doi":"10.3109/10799899309073645","DOIUrl":"https://doi.org/10.3109/10799899309073645","url":null,"abstract":"<p><p>Using living cells or tissues 31P nuclear magnetic resonance (NMR) spectroscopy can uniquely provide a real-time panoramic view of the major intracellular phosphate metabolites and continuously monitor changes in their concentrations. Hormone regulated cascades in many instances influence intracellular phosphate metabolism at various levels. Regulation of the respective key control enzymes is often mediated by second messengers, themselves phosphate metabolites, such as 3'5' cyclic adenosine monophosphate (cAMP), 3'5' cyclic guanosine monophosphate (cGMP), and inositol Tris phosphate (IP3). Moreover, protein phosphorylation/dephosphorylation reactions are also extensively involved in hormonal regulation. The consequent changes in the rates of the regulated processes, best known in the cases of glycogen and fat metabolism, are reflected in the rates of ATP synthesis and utilization as well as in the levels of phosphate containing intermediary metabolites. In this paper we describe an application of non-invasive 31P NMR spectroscopy for the examination of a signal transducing process and responsive cascades regulated by the melanocyte stimulating hormone (MSH) in live cultured M2R mouse melanoma cells. With proper modifications this technical approach can be adapted to the study of other cell systems.</p>","PeriodicalId":16948,"journal":{"name":"Journal of receptor research","volume":"13 1-4","pages":"55-68"},"PeriodicalIF":0.0,"publicationDate":"1993-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799899309073645","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18685328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}