Receptor最新文献

{"title":"The molecular mechanism of the action of the pharmacological doses of glucocorticoids. Studies on the low-affinity glucocorticoid receptor.","authors":"Y Y Le,&nbsp;R B Xu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The low-affinity glucocorticoid binding sites (LAGS, kDa 1-10 mumol/L) with glucocorticoid specificity were demonstrated in hepatic cytosol of rats. The induction of tyrosine aminotransferase (TAT) activity in primary cultures of rat hepatocytes by high concentration (10 mumol/L) of hydrocortisone (F) could be completely inhibited by RU486, the competitive antagonist of glucocorticoid receptor, indicating that the induction of TAT by high concentrations of F is mediated by LAGS, therefore, LAGS may be referred to as low-affinity glucocorticoid receptor (GRL). In order to study the effect of GC on GRL, the concentration of glucocorticoids (GC) in plasma was maintained over 1 mumol/L for 3 d by subcutaneous injection of F in polyvinyl alcohol into rats. The binding capacity (Ro) of high-affinity glucocorticoid receptor (GRH) decreased significantly 1 h after injection and maintained at low level, whereas the Ro of GRL increased at 1, 24, and 48 h after injection. Thus, it may be concluded that GC can downregulate GRH but upregulate GRL. These results strongly suggest that the action of pharmacological doses of GC may be mediated by GRL.</p>","PeriodicalId":21112,"journal":{"name":"Receptor","volume":"5 1","pages":"63-9"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18618325","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":"Growth hormone (GH)-induced tyrosine-phosphorylated proteins in cells that express GH receptors.","authors":"P A Harding,&nbsp;X Z Wang,&nbsp;J J Kopchick","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have shown previously that growth hormone (GH)-induced tyrosine phosphorylation of a 95-kDa protein in mouse L-cells stably transfected with the GH receptor. In addition to induction of pp95, we have established that GH also induces tyrosine phosphorylation of a 42-kDa protein and a 130-kDa protein, as detected with phosphotyrosine antibodies. A time course of tyrosine phosphorylation on GH treatment indicates that within the GH signal transduction cascade, tyrosine phosphorylation of pp95 occurs by 1 min, whereas tyrosine phosphorylation of pp42 was not detected until 5 min. Additionally, the concentration of GH needed to stimulate tyrosine phosphorylation of pp42 was greater than that required for pp95. The pp42 protein comigrates with a 42-kDa protein identified as extracellular signal-regulated kinase 2 (ERK2). Growth factors, such as FGF, PDGF, IGF-I, and insulin, induce tyrosine phosphorylation of pp42 in pGHR-W10 cells and in 3T3-F442A preadipocytes; however, they are unable to induce pp95. These results suggest that GH induction of tyrosine-phosphorylated pp42 may represent a common signal transduction point of various growth factors, including GH, whereas tyrosine phosphorylation of pp95 is GH specific.</p>","PeriodicalId":21112,"journal":{"name":"Receptor","volume":"5 2","pages":"81-92"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18586732","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":"Cytokine signal transduction.","authors":"C Schindler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The normal growth, maturation, and activation of cells in most tissues requires stimulation with a defined set of growth factors. These growth factors bind cognate receptors on surface of target cells, and stimulate specific intracellular signals. Many of these signals culminate in the induction of a ligand-specific set of genes. The characterization of signaling components that mediate the induction of genes in response to IFNs has led to the identification of a new signal transduction pathway. The components of this pathway are able to rapidly transduce high fidelity signals directly from the receptor to the nucleus. Recently, many other cytokines and growth factors, including IFN-alpha, IFN-gamma, IL-6, and prolactin (PRL), have been shown to induce new genes through the same signaling paradigm.</p>","PeriodicalId":21112,"journal":{"name":"Receptor","volume":"5 1","pages":"51-62"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18618324","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":"Quantitative determination of recombinant fibroblast growth factor receptor in baculovirus-infected insect cell cultures.","authors":"J L Duke,&nbsp;S P Sheth,&nbsp;A T Nahapetian","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Members of the fibroblast growth factor protein family are involved in several biologically important processes, including angiogenesis, wound healing, and tumor growth and metastasis. Interactions of basic fibroblast growth factor (bFGF) and its receptors are of considerable pharmacological importance. Attempts were made to produce gram quantities of a soluble extracellular form of basic fibroblast growth factor receptor type 1 (bFGFR1) in order to study the energetics of its interaction with bFGF. The aim of the present study was to develop a method for monitoring changes in concentration of bFGFR1 during its production by large-scale baculovirus-infected insect cell culture. A simple reverse-phase high-performance liquid chromatographic assay was developed for direct determination of the soluble receptor secreted into insect cell-culture media. The method permitted cell-culture samples containing varying amounts of fetal calf serum and bFGFR1 (10-30 mg/L) to be analyzed without prior purification. The assay was linear for added receptor in the range of 1-7 micrograms.</p>","PeriodicalId":21112,"journal":{"name":"Receptor","volume":"4 3","pages":"135-41"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18812325","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":"Expression of alpha 2-adrenergic receptor genes in rat tissues.","authors":"H S Blaxall,&nbsp;N A Hass,&nbsp;D B Bylund","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Alpha-2 adrenergic receptor subtypes are coded for by three genes. Pharmacologically alpha 2 adrenergic receptors can be classified into four subtypes: alpha 2A, alpha 2B, alpha 2C, and alpha 2D. Although pharmacologically distinct, the amino acid sequences of the alpha 2A and alpha 2D subtypes are approx 90% identical and have not been detected in a single species. Thus, they should be considered species orthologs and may be referred to as alpha 2A/D. The tissue distribution of the mRNAs for the rat alpha 2A/D, alpha 2B, and alpha 2C was analyzed utilizing RNase protection assays with probes directed to the third cytoplasmic loops. Alpha-2 adrenergic receptor mRNA was found in all tissues tested. Kidney, brain, and spinal cord had transcripts for all three subtypes. Only one mRNA subtype was detected in several tissues. Aorta and spleen had only alpha 2A/D mRNA, whereas heart and liver had only alpha 2B mRNA. All other tissues had two alpha 2 adrenergic subtype transcripts present. In contrast to the rat CNS, which contains predominantly alpha 2A/D and alpha 2C mRNA with little alpha 2B mRNA, peripheral tissues contain predominantly alpha 2A/D and alpha 2B mRNA with little alpha 2C mRNA.</p>","PeriodicalId":21112,"journal":{"name":"Receptor","volume":"4 3","pages":"191-9"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18812329","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":"Autoregulation of corticosteroid receptors. How, when, where, and why?","authors":"T J Schmidt,&nbsp;A S Meyer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The corticosteroid receptors, including the glucocorticoid and mineralocorticoid receptors (GR and MR, respectively), are subject to ligand-mediated autoregulation like other members of the steroid receptor gene superfamily. Since it is the level of expression of these closely related intracellular receptors that determines cellular sensitivity to adrenal glucocorticoid and mineralocorticoid hormones, homologous as well as potential heterologous regulation of GR and MR levels constitute physiologically important homeostatic events. Although these autoregulatory responses are often exhibited in the form of receptor down-regulation (negative autoregulation), hormone-mediated up-regulation (positive autoregulation) has also been documented. Clearly, the extent as well as direction of hormone-mediated autoregulation of corticosteroid receptors vary considerably between different target tissues and cell types and may be altered during development or as a consequence of aging or disease state. Although historically the homologous as well as heterologous regulation of GR and MR were evaluated exclusively at the ligand binding levels, the cloning of the genes for these corticosteroid receptors has facilitated detailed analysis of hormonal regulation at the message and protein levels. Data generated in numerous laboratories have demonstrated that this regulation may be mediated at one or more molecular levels, including: the transcriptional level, as evidenced by the ability of ligand-receptor complexes to decrease the rate of receptor gene transcription; the posttranscriptional level, as evidenced by the ability of some ligands to alter the stability of their own receptor message; and at the posttranslational level, as evidenced by the ability of agonists to shorten the half-life of their own receptor protein. In this review we have focused on several basic questions (how, when, where, and why?) concerning this hormonal regulation of corticosteroid receptors. Clearly, many of these key questions concerning autoregulation of GR and MR levels remain unanswered and further studies in this area will enhance our understanding of the mechanisms involved in these cellular events.</p>","PeriodicalId":21112,"journal":{"name":"Receptor","volume":"4 4","pages":"229-57"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18890758","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":"Pharmacological profiles of contractile endothelin receptors in guinea pig hilar bronchus.","authors":"Y Kizawa,&nbsp;Y Nakajima,&nbsp;J Nakano,&nbsp;H Uno,&nbsp;M Sano,&nbsp;H Murakami","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Characterization of the receptors mediating contractions to endothelin-1 (ET-1), endothelin-3 (ET-3), sarafotoxin S6c (STXc), or IRL 1620 in isolated epithelium-denuded hilar bronchus of guinea pig using as antagonists BQ-123 (ETA receptor-selective) and Ro 46-2005 (ETA/B nonselective) was investigated. ET-1, ET-3, STXc, and IRL 1620 produced only contraction, and their concentration-response curves were obtained at the same concentration range (10(-10)-10(-7) M). The potency order was the following: STXc = ET-3 = ET-1 > IRL 1620. BQ-123 (10(-5)M) had no marked effect on the contraction induced by ET-3 or STXc, whereas it attenuated the response induced by high concentration of ET-1 (3 x 10(-8)-10(-7)M). The contraction induced by IRL 1620 was antagonized by BQ-123 (3 x 10(-6)-10(-5)M). Ro 46-2005 (10(-5)M) failed to inhibit the responses to ET-1 and ET-3. Ro 46-2005 (10(-5)M) slightly, but significantly, shifted the concentration-response curve for STXc to the right (pKB = 4.94 +/- 0.10, n = 7), and the maximum response was potentiated to about 127%. The curve for IRL 1620 was shifted in parallel by Ro 46-2005 (3 x 10(-6)-10(-5)M) to the right (mean pKB = 6.35 +/- 0.09, n = 8). These results suggest that ETB receptors primarily mediate contraction to ET-1, ET-3, STXc, and IRL 1620, and the relative inhibitory activities of ET antagonists vary with the agonist used. However, ET-1 and ET-3 might also activate non-ETB receptor or unknown mechanisms.</p>","PeriodicalId":21112,"journal":{"name":"Receptor","volume":"4 4","pages":"269-76"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18890760","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":"The androgen receptor in the testicular feminized (Tfm) mouse may be a product of internal translation initiation.","authors":"W W He,&nbsp;J K Lindzey,&nbsp;J L Prescott,&nbsp;M V Kumar,&nbsp;D J Tindall","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Androgen insensitivity in the testicular feminized (Tfm) mouse is caused by frame-shift mutation in the androgen receptor (AR) mRNA, which results in a stop codon in the amino terminus. Despite this mutation, a smaller sized protein corresponding to the DNA- and steroid-binding domain of the AR can be synthesized from the cloned Tfm AR cDNA by in vitro translation. The Tfm AR construct was demonstrated to express a protein capable of binding androgen with an affinity similar to the cloned wild-type AR. Although the Tfm AR product failed to transactivate mouse mammary tumor virus-long terminal repeat (MMTV-LTR) promoter when low concentrations (100 ng) of Tfm AR vector were cotransfected, higher concentrations (5000 ng) resulted in a residual amount of transactivation, suggesting lower level transactivating capabilities. By cotransfecting the Tfm AR expression vector with the wild-type receptor, it was demonstrated that the product of the Tfm AR gene is capable of inhibiting the transactivation activity of the wild-type receptor. These data suggest that although the Tfm AR mRNA fails to produce a full-length AR because of the frame-shift mutation, a smaller protein capable of binding both steroid and DNA can be produced by translation from an internal initiation codon. This product could account for the low levels of androgen-binding activity detected previously in the Tfm mouse.</p>","PeriodicalId":21112,"journal":{"name":"Receptor","volume":"4 2","pages":"121-34"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18946888","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":"Opioid binding in giant toad and goldfish brain.","authors":"A I Brooks,&nbsp;K M Standifer,&nbsp;J Cheng,&nbsp;G Ciszewska,&nbsp;G W Pasternak","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Opiate receptor expression in phylogenetically different species has played an important role in the study of opioid receptor pharmacology. Total opioid binding measured with the nonselective ligand 3H-diprenorphine reveals a Bmax of 21.7 +/- 1.37 fmol/mg tissue wet wt and a KD of 0.17 +/- 0.03 nM in Bufo marinus (giant toad), as well as a Bmax of 18.17 + 0.41 fmol/mg tissue wet wt and a KD of 0.47 +/- 0.18 nM in Carassius auratus (goldfish). Despite the similar levels of 3H-diprenorphine binding, the composition of binding subtypes in the two species differs. Approximately 30% of total binding corresponds to mu receptors in both species, whereas neither kappa 1 nor delta binding can be detected. However, the remaining 70% of binding differs between the toad and goldfish. In the toad, the non-mu binding corresponds to kappa 2 sites, whereas in the goldfish, the non-mu binding corresponds to kappa 3 sites. The sites can be distinguished biochemically, as well as pharmacologically. After affinity labeling the sites with 3H-NalBzoH, the retention times on an ion-exchange column differ for the peaks of kappa binding in the two species. Although Bufo marinus (giant toad) and Carassius auratus (goldfish) brains express kappa and mu opioid binding, the kappa subtypes in these two species differ.</p>","PeriodicalId":21112,"journal":{"name":"Receptor","volume":"4 1","pages":"55-62"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19032828","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":"Orphan receptor HNF-4 and liver-specific gene expression.","authors":"F M Sladek","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":21112,"journal":{"name":"Receptor","volume":"4 1","pages":"64"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19032829","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}