Receptors and Channels (Recept Channel )

Description

Receptors and Channels publishes papers covering all aspects of original research on receptors and ion channels and the related signalling elements (including G-proteins). These can be at the levels of molecular biology and genetics, biochemistry, physical analysis, molecular modelling, immunochemistry, molecular pharmacology and electrophysiology. The journal accepts investigations at the molecular level on distribution, function, gene mapping, regulation and development. Also within its scope are the molecular study of membrane transporters, drug design in relation to receptors and channels, and the relationships of receptor and channel activity to disease states.

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  • Website
    Receptors and Channels website
  • Other titles
    Receptors & channels (Online), Receptors & channels
  • ISSN
    1060-6823
  • OCLC
    51679621
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publications in this journal

  • Receptors and Channels 12/2011; 8(1).
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    ABSTRACT: The human g 1 -adrenoceptor ( g 1 AR) exists in several isoforms and activates adenylyl cyclase (AC) via G s -proteins. The Arg389-isoform of the g 1 AR ( g 1 AR-R389) expressed in CHW cells is much more efficient than the Gly389 isoform of the g 1 AR ( g 1 AR-G389) at stabilizing the ternary complex and activating AC (Mason et al. 1999). The g 1 AR-G389 fused to the G s f splice variants G s f L or G s f S is efficient at stabilizing the ternary complex and activating AC (Wenzel-Seifert et al. 2002). Here, we show that g 1 AR-R389-G s f fusion proteins and g 1 AR-G389-G s f fusion proteins are similarly efficient at stabilizing the ternary complex and activating AC. In terms of agonist efficacies and agonist potencies in the [ 35 S]guanosine 5'- O -(3-thiotriphosphate) binding assay, g 1 AR-R389-G s f fusion proteins and g 1 AR-G389-G s f fusion proteins are similar, too. Our present data fit to an increasing number of clinical studies that failed to detect physiology- or pathology-related functional differences between g 1 AR-R389 and g 1 AR-G389.
    Receptors and Channels 12/2011; 9(5).
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    ABSTRACT: After transient transfection of an hNav1.4-L443C/A444W mutant clone, HEK-293 cells exhibited large inactivation-deficient Na+currents. We subsequently established a stable cell line expressing robust inactivation-deficient Na+currents. Persistent late Na+currents were far more sensitive to block by class 1 anti-arrhythmic flecainide, mexiletine, propafenone, and amiodarone at 10 microM than peak Na+currents. Such results support a hypothesis that persistent late Na+currents are in vivo targets for class 1 anti-arrhythmic drugs at their therapeutic plasma concentrations. Stably transfected HEK-293 cells expressing robust inactivation-deficient Na+currents will likely be suitable for screening novel drugs that target persistent late Na+currents selectively.
    Receptors and Channels 05/2004; 10(3-4):131-8.
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    ABSTRACT: Activation of the receptor tyrosine kinase (RTK), insulin (IRK) or neurotrophin B (TrkB), was characterized and compared in olfactory bulb neuron (OBN) cultures from Sprague Dawley rats and sv129 B6 mice. Current suppression attributed to modulation of the delayed rectifier, Kv1.3, a voltage-gated potassium (Kv) channel of the Shaker family, was observed following acute application of the growth factors, insulin or brain-derived neurotrophic factor (BDNF), to mitral cells of either rodent model. Using site-directed mutagenesis of putative tyrosine phosphorylation recognition motifs in the channel, we find that stimulation of Kv1.3 with these growth factors causes multiple phosphorylation, albeit via different residue combinations that are RTK specific.
    Receptors and Channels 02/2004; 10(1):25-36.
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    ABSTRACT: Levels of the 19 proteinous amino acids and total free amino acids were assayed by gas-liquid chromatography in cytosols of rat atrial and ventricular muscle cardiomyocytes. The tissues were assayed after the rats had been exposed to the cardioactive drugs digoxin, caffeine, and isoproterenol, each having different mechanisms of action. We demonstrated that, in the atrial and ventricular cardiac muscle cytosol of control (untreated) rats, arginine, glutamine, and cysteine existed in their highest levels: 35.1% and 17.6%; 14.8% and 51.6%; 9.9% and 0.25% of the total free amino acids, respectively. The levels of the other amino acids in the atrial and ventricular cardiac muscle cytosols ranged between 0.1% and 10.0% of the total free amino acids. Digoxin, caffeine, and isoproterenol significantly reduced the total amount of cytosolic free amino acids in the atrial heart muscle cytosol to 7.6%, 9.0%, and 9.2% of the control value (100%), and in the ventricular heart muscle cytosol to 31.1%, 43.2%, and 28.3% of the control. The three drugs tested changed the cytosols' levels of arginine, cysteine, tryptophane, asparagine, and tyrosine in atrial and ventricular heart muscle cytosol, as compared to the control groups (calculated as a percent of the total free amino acids in the experimental groups). The role of proteinous amino acids in the function of the heart muscle and in the mechanism of action of these drugs on the mammalian heart is discussed.
    Receptors and Channels 02/2004; 10(2):91-7.
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    ABSTRACT: Sex and age influence morphine analgesia in humans and animals. Mature rats show greater morphine analgesia in males than in females. Ultra-low doses of naltrexone enhance morphine analgesia. In mature rats (18-22 weeks), naltrexone (0.002-2.0 mg/kg)-morphine (2 mg/kg) cotreatment enhanced morphine analgesia in females, an effect inversely related to naltrexone dose. Conversely, in mature male rats, naltrexone tended to decrease morphine analgesia with increasing dose. In young rats (8-10 weeks), morphine analgesia was unrelated to sex and in both sexes the naltrexone-morphine interaction was negligible. These data show that dose, age, and sex alter the naltrexone-morphine interaction in rats.
    Receptors and Channels 02/2004; 10(2):73-81.
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    ABSTRACT: Tissue levels of nineteen amino acids and total free amino acids, were assayed by gas-liquid chromatography in cytosols of rat atrial and ventricular muscle cardiomyocytes. The tissues were assayed after the rats had been administered IP with the three cardioactive drugs, exerting a significant effect on their heart action: propranolol, pentylenetetrazol and reserpine. It was demonstrated that while in the atrial and ventricular cardiac muscle cytosols of control rats, arginine, glutamine and cysteine were detected in high levels (35.1% and 17.6%; 14.8% and 51.6%; 9.9% and 0.25% of the total free amino acids, respectively), all three drugs significantly reduced the total amounts of cytosolic free amino acids in both atrial and ventricular heart muscles. All three drugs (with reserpine in particular) modified the levels of arginine, cysteine, phenylalanine, tryptophan, isoleucine and tyrosine. The role of these amino acids in the heart muscle cytosol, and their involvement in the mechanism of action of these three cardioactive drugs, is discussed.
    Receptors and Channels 02/2004; 10(2):83-90.
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    ABSTRACT: To explore whether cholecystokinin-B/gastrin receptor (CCKBRwt) gene and its alternative splicing variant preserving intron 4 (CCKBRi4sv) are expressed in human gastric carcinoma cell line and tissue, we detect mRNA expression of CCKBRwt and CCKBRi4sv in 30 gastric carcinoma and their corresponding normal tissues, 10 gastritis, and 2 autopsied normal stomach specimens as well as in a gastric carcinoma cell line SGC-7901 cells by RT-PCR and sequencing. The results revealed that human normal, inflammatory, and malignant gastric tissues simultaneously expressed the classical and alternative splicing cholecystokinin-B/gastrin receptor genes. The alternative splicing variant contains the intron 4 of cholecystokinin-B/gastrin receptor gene.
    Receptors and Channels 02/2004; 10(5-6):185-8.
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    ABSTRACT: Multivariate methods and molecular properties are utilized to show similarity of pyridine-3-carboxylic acid (nicotinic acid) to seven drugs that penetrate the central nervous system. Multivariate methods applied include cluster analysis, discriminant analysis, correspondence analysis, self organizing tree algorithm (SOTA) analysis, factor analysis, and principal component analysis. Numerical values of properties for nicotinic acid showed very high correlation with the values from dihydropyridine, barbital, metharbital, phenobarbital, methohexital, 4-aminohex-5-enoic acid, and (4-chlorophenyl)(5-fluoro-2-hydroxyphenyl)methanone. Descriptive statistics of property values for these drugs showed overlapping numerical values for partition coefficients, index of refraction, and nOnN. Principal component analysis and factor analysis of molecular properties showed that nicotinic acid is highly similar to dihydropyridine as well as to other members of this group of drugs. Applying cluster analysis utilizing standard euclidean distance with single linkage and centroid linkage showed that nicotinic acid is highly similar to dihydropyridine and both are consistently grouped into the identical cluster (indicating high similarity). Both nicotinic acid and dihydropyridine show zero violations of the Rule of 5, which indicates good bioavailability characteristics. Discriminant analysis of molecular properties for these eight compounds could not demonstrate differentiation between nicotinic acid and dihydropyridine within the properties applied, this indicating high level of similarity. Neural cluster analysis of molecular properties showed that nicotinic acid and dihydropyridine are included into the same cluster (indicating very strong similarity). SOTA analysis also placed nicotinic acid and dihydropyridine into the same cluster unit. SOTA analysis of molecular properties indicates high similarity between nicotinic acid and dihydropyridine. Correspondence analysis was performed on the molecular properties and showed that there exists considerable association between dihydropyridine and nicotinic acid. Multiple regression analysis of these molecular properties produced a mathematical equation to predict the formula weight of similar compounds for use as drug carriers.
    Receptors and Channels 02/2004; 10(2):61-71.
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    ABSTRACT: In order to evaluate the methylotrophic yeast Pichia pastoris as means for high-yield production of homogenous D(2S) receptor protein, we have expressed the unmodified D(2S) receptor and various D(2S) receptor fusion constructs under the transcriptional control of the highly inducible promotor of the P. pastoris alcoholoxidase 1 gene in strain SMD1163. Fusion of the D(2S) receptor gene to the alpha-factor preprosequence proved to be essential for receptor production. For the receptor fusion constructs a gene dosage of more than two copies per cell increased production levels three- to sixfold. Adding various dopaminergic ligands to the induction medium increased yields up to tenfold, reaching 51,500 +/- 5700 receptors/cell. Immunoblot analysis of the effect of tunicamycin on D(2S) receptor fusion proteins and immunoprecipitation of metabolically labeled wild-type and glycosylation-deficient D(2S) receptor fusion proteins revealed that the high-mannose-type glycosylation of the D(2S) receptor prevents cleavage of the alpha-factor prosequence by the Kex2 endopeptidase. Abolishing glycosylation restored correct processing. Immunogold electron microscopy showed that recombinant yeast cells overproducing the D(2S) receptor developed membrane stacks harboring the receptor protein. The pharmacological profile of the recombinant D(2S) receptor was similar to that reported for neuronal D(2) receptors independent of glycosylation and processing. In conclusion, the D(2S) receptor can readily be produced in P. pastoris with high yield suitable for receptor purification and future structural studies.
    Receptors and Channels 02/2004; 10(1):37-50.
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    ABSTRACT: G protein-coupled receptors induce intracellular signals via interaction of with cytosolic/peripheral membrane proteins, mainly G proteins. There has been much debate about the mode of interaction between the receptors, G proteins and effectors, their mobility and the ways of determining the specificity of interaction. Additional complexity has been added to system upon the discovery of i) coupling of single receptors to several G proteins and ii) active direction of this by different ligands (stimulus trafficking). These data suggest that the most primary unit in the signal transduction is the receptor complexed with a specific G protein, making the investigation of the mechanism of receptor-G protein selection and interaction even more important. In this review, I will summarize the general knowledge of receptor interaction with G proteins and effectors and the ways of investigating this.
    Receptors and Channels 02/2004; 10(5-6):167-83.
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    ABSTRACT: When Chinese hamster ovary cells transfected with the gene for M(3)-muscarinic receptors were stimulated with carbachol continuously for 30 min, the response at the end of the stimulation period was about 20% of the early response (2-3 min after the start of the stimulation). Long-term treatment of the cells with phorbol ester abolished the response completely while desensitization was significantly reduced upon pre-treatment of the cells with GF109203X, antisense oligonucleotide against the alpha-isoform of protein kinase C and wortmannin. We conclude that in the Chinese hamster ovary expression system, desensitization of M(3)-muscarinic receptors is dependent on a fast feedback loop including the alpha-isoform of protein kinase C.
    Receptors and Channels 02/2004; 10(1):1-10.
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    ABSTRACT: Allosterism, whereby small molecule ligands produce global changes in the conformations of receptors, is a powerful mechanism for drug effect. This is illustrated by the recent data describing CCR5 antagonists as blockers of HIV infection. Allosteric effects are described in terms of a change in the tertiary conformation of the receptor. This paper outlines some unique features of allosteric antagonists as new drug entities. These include the fact that allosteric ligands have texture in antagonism (not all allosterically blocked receptors are alike), allosteric blockade is probe dependent (not all agonists and radioligands are blocked equally), and the fact that allosteric binding involves a separate site on the receptor may have relevance to duration of effect and selectivity. Dissociation between receptor function and binding also can be encountered with allosteric ligands.
    Receptors and Channels 02/2004; 10(2):51-60.
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    ABSTRACT: A novel, membrane potential sensitive dye and a fluorescence imaging plate reader (FLIPR) have been used to characterize the pharmacological properties of rat Na(v)1.8 voltage-gated sodium channels (VGSC) in parallel with rat Na(v)1.2a and human Na(v)1.5 VGSC subtypes, respectively. The sensitivity of recombinant Na(v)1.2a-CHO, Na(v)1.5-293-EBNA, and Na(v)1.8-F-11 cells to VGSC activators was subtype dependent. Veratridine evoked depolarization of Na(v)1.2a-CHO and Na(v)1.5-293-EBNA cells with pEC(50) values of 4.78 +/- 0.13 and 4.84 +/- 0.12, respectively (n = 3), but had negligible effect on Na(v)1.8-F-11 cells (pEC(50) < 4.5). Type I pyrethroids were without significant effect at all subtypes. In contrast, the type II pyrethroids deltamethrin and fenvalerate evoked direct depolarization of Na(v)1.8-F-11 and Na(v)1.5-293-EBNA cells. Deltamethrin potentiated the veratridine-evoked response in Na(v)1.8-F-11 cells by > or =20-fold, in contrast to a <or =3-fold potentiation of the response in Na(v)1.2a, and Na(v)1.5 cells. Tetrodotoxin (TTX) inhibited VGSC activator-evoked depolarization of Na(v)1.8-F-11 cells with a biphasic concentration-response curve. The calculated pIC(50) values were 8.05 +/- 0.25 (n = 4) and 4.32 +/- 0.21 (n = 4), corresponding to TTX inhibition of endogenous TTX-sensitive (TTX-S), and recombinant Na(v)1.8 TTX-resistant (TTX-R) VGSCs, respectively. With the exception of TTX, the potencies of a number of ion channel blockers for the Na(v)1.8, Na(v)1.2a, and Na(v)1.5 VGSC subtypes were similar. In summary, these high-throughput FLIPR assays represent a valuable tool for the determination of the relative potencies of compounds at different VGSC subtypes and may prove useful for the identification of novel subtype-selective inhibitors.
    Receptors and Channels 02/2004; 10(1):11-23.
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    ABSTRACT: Recombinant baculoviruses, in which the insect cell-specific polyhedrin promoter has been replaced with a mammalian cell-active expression cassette (BacMam viruses), are efficient gene delivery vehicles for many mammalian cell types. BacMam viruses have been generated for expression of G protein-coupled receptors (GPCRs) and used to establish Ca2+mobilization assays in HEK-293 human embryonic kidney cells and U-2 OS human osteosarcoma cells. U-2 OS cells are highly susceptible to BacMam-based gene delivery and lack many of the endogenous receptors present on HEK-293 and other mammalian cell lines typically used for heterologous expression of GPCRs. U-2 OS cells were found to have a null background for muscarine, ADP, ATP, UTP, UDP, and lysophosphatidic acid (LPA). Consequently, U-2 OS cells transduced with BacMam constructs encoding the muscarinic acetylcholine receptors (M1, M2, M3, M4, and M5subtypes), the P2Y receptors (P2Y1, P2Y2), or the LPA receptors (EDG-2, EDG-7) were used for the establishment of whole-cell Ca2+mobilization assays, assays that cannot readily be established in HEK-293 cells. U-2 OS cells were susceptible to simultaneous expression of multiple genes delivered by BacMam vectors. In U-2 OS cells the functional expression of the Gi-coupled M2and M4receptors was dependent on co-expression of the receptor and a G protein chimera, both of which were delivered to the cells via BacMam viruses. The use of U-2 OS cells and BacMam-based gene delivery has facilitated development of whole-cell-based GPCR functional assays, especially for P2Y, muscarininc acetylcholine, and LPA receptors.
    Receptors and Channels 01/2004; 10(3-4):117-24.
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    ABSTRACT: The initial objective of this work was to examine the effects of an antibody (Anti-G21V) directed against the second extracellular loop of human heart 5-HT4 receptors expressed in Chinese hamster ovary (CHO) cells. The antibody anti-G21V had no effect upon either basal cAMP-or 5-HT-evoked increases in cAMP in CHO cells, whereas it had shown an agonist-like effect in COS-7 cells. Analysis of agonist fractions of h5-HT4(e) receptors in CHO and COS-7 cells revealed that equilibrium constant could underlie the different responses of the receptor toward the anti-G21V antibody. Therefore, different expression systems could give rise to functional differences in 5-HT4 receptor behavior.
    Receptors and Channels 01/2004; 10(3-4):125-9.
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    ABSTRACT: In human atrial myocytes, serotonin rather than sympathetic, stimulation is more frequently associated with atrial fibrillation. So does the arrhythmogenic effect of serotonin result from the mechanism of action of the receptor or the context of its action upon cardiac myocytes? The capacity of agonists to produce cAMP followed the sequence 5-HT < Iso < Forskolin to increase ICaL with 5-HT = Iso = Forskolin. The simultaneous application of threshold concentrations of 5-HT and Iso maximally increased ICaL. We will show that the effect of 5-HT upon human atrial myocytes is an imbalance between low production of cAMP and maximal activation of ICaL.
    Receptors and Channels 01/2004; 10(5-6):159-65.