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At least 163 records · Page 9Linked to original sources
PubMed1986

H1-histamine receptors on human astrocytoma cells.

The H1-histamine receptor antagonist [3H]mepyramine bound with high affinity (Kd = 3-5 nM) to membranes derived from 1321N1 human astrocytoma cells. The H1-receptor antagonists triprolidine and diphenhydramine inhibited [3H]mepyramine binding with Kj values of 1-5 nM, whereas the Kj of the H2-histamine receptor antagonist cimetidine was greater than 100 microM. Histamine also inhibited [3H]mepyramine binding to 1321N1 cell membranes, and the histamine inhibition curve was shifted to the right and steepened in the presence of 1 microM guanosine 5'-O-(3-thiotriphosphate). Treatment of 1321N1 cells with pertussis toxin had no effect on the capacity of histamine to inhibit [3H]mepyramine binding either in the absence or presence of guanosine 5'-O-(3-thiotriphosphate). Therefore, agonist-occupied histamine receptors in these cells apparently interact with a guanine nucleotide regulatory protein that is not the inhibitory guanine nucleotide regulatory protein of adenylate cyclase. Although adenylate cyclase activity was not affected by histamine in a cell-free preparation, incubation of 1321N1 cells with histamine resulted in an attenuation of cyclic AMP accumulation. Analysis of cyclic AMP degradation in the presence of histamine indicated that the effects of histamine on cyclic AMP accumulation are mediated through activation of phosphodiesterase. This idea was supported by the fact that the phosphodiesterase inhibitor 1-isobutyl 3-methylxanthine blocked attenuation of cyclic AMP accumulation by histamine in a noncompetitive manner. Histamine also markedly increased phosphoinositide breakdown and 45Ca2+ efflux in 1321N1 cells. These histamine-induced effects apparently are mediated through H1-receptors, since triprolidine, but not cimetidine, potently inhibited histamine action. As for histamine interaction with its receptor, pertussis toxin had no effect on histamine-induced phosphoinositide breakdown, 45Ca2+ efflux, or attenuation of cyclic AMP accumulation. Taken together, these data indicate that 1321N1 human astrocytoma cells are a useful model system for the study of H1-histamine receptors and the biochemical responses mediated through these receptors.

1-Methyl-3-isobutylxanthine↗
PubMed1984

[Synthesis and analysis of potent cyclic analogs of the ACTH active center].

Linear and cyclic analogues of the specific active center of the ACTH molecule have been synthesized, viz. [Lis5]ACTH-(5-10)-, [Lys5, cyclo (Gly10----epsilon Lys5)]-ACTH-(5-10)-hexapeptides, [Lys5 (Gly)]ACTH-(5-10)- and [Lys5, Gly11, cyclo (Gly11----epsilon Lys5)]-ACTH-(5-11)-heptapeptides. The cyclic structures are fixed by covalent bond between the COOH-group of the C-terminal glycine and epsilon-amino group of a lysine residue. Azide method, DCC/HOBT or pentafluorophenyl esters are used for fragment coupling, while cyclization is achieved by means of diphenylphosphoryl azide or pentafluorophenyl esters. Cyclic compounds are 2-3 orders of magnitude more active than their linear counterparts as revealed by assaying their melanocyte-stimulating activity in vitro on frog skin. Only the title heptapeptide possesses a steroidogenic activity similar to that of ACTH-(5-10)-hexapeptide. The results obtained are in accord with the idea implying the formation in the hormone-receptor complexes of quasi-cyclic structures in the region of the specific active center of ACTH molecule.

Adrenocorticotropic Hormone↗
PubMed1983

[Identification and analysis of hydrogenated cyclic monomeric acids in the hepatic lipids of rats ingesting heated linseed oil].

In a short-term (15 days) experiment, weanling Wistar rats were given diets at weaning containing 10% of different linseed oils: fresh linseed oil (lot F), linseed oil heat polymerized at 275 degrees C for 12 h under nitrogen (lot T) and linseed oil oxidized in the presence of air at 200 degrees C for 100 h (lot O). We analyzed the fatty acids of total liver lipids and assayed the hydrogenated cyclic monomeric acids and identified them by using a combination of gas-liquid chromatography and mass spectrometry. Compared to lot F animals, those of lots T and O showed considerable hepatic hypertrophy but total liver lipids were not increased. However, the usual fatty acid composition of these lipids was modified: the level of several monounsaturated (16: 1, 18: 1) and polyunsaturated (mainly 20: 4n - 6) fatty acids was increased in lots T and O, which could result in increased activity of the enzymatic systems (desaturases) biosynthesizing them. Moreover, cyclic monomeric acids from heated oils were deposited at a 10 times higher concentration in the liver of lot T animals than in that of lot O animals. The significance of these changes has been discussed.

Animals↗
PubMed1998

Self-Assembling Synthesis of Cyclic Tri- and Tetranuclear Cobalt(III) Complexes Bridged by Purine-6-thione and Their Characterization by Electrospray Mass Spectrometry and X-ray Crystal Analysis.

The cyclic multinuclear complexes [Co(n)()(L-N,S,N')(n)()(tacn)(n)()](n)()(+) (L = purine-6-thiones; tacn = 1,4,7-triazacyclononane) were synthesized through self-assembly of the mononuclear complex [Co(HL-N,S)Cl(tacn)](+) based on the multidentate bridging ability of purine-6-thione. Three kinds of purine-6-thione ligands were used: 9H-purine-6(1H)-thione (H(2)put), 2-amino-9H-purine-6(1H)-thione (H(2)aput), and 3,6-dihydro-6-thioxo-9H-purin-2(1H)-one (H(3)tpuo). The complexes [Co(n)()(L-N,S,N')(n)()(tacn)(n)()](n)()(+), n = 3 and 4 for put and n = 4 for aput and Htpuo, were characterized by NMR spectroscopy, electrospray ionization mass spectrometry (ESI-MS), and X-ray crystal structure analysis. ESI-MS proved to be a very powerful tool for determining the nuclearity (n value) unambiguously. X-ray crystal structure analyses of [Co(4)(put)(4)(tacn)(4)](CF(3)SO(3))(4).12H(2)O [triclinic, P&onemacr; (No. 2)] and [Co(4)(aput)(4)(tacn)(4)]Cl(4).16H(2)O [monoclinic, C2/c (No. 15)] reveal that all purinethione ligands act as tridentate ligands via S(6)/N(7) chelation and the N(9) bridge and both tetranuclear complexes adopt the cyclic S(4) structure which is stabilized by four intramolecular hydrogen bonds between N(3) and H-N(tacn). The trinuclear complex [Co(3)(put)(3)(tacn)(3)](3+) having the C(1) structure was optically resolved. Stereochemistry for the cyclic molecular boxes containing chiral octahedral ions is developed.

Journal Article↗
PubMed1999

PKA from Saccharomyces cerevisiae can be activated by cyclic AMP and cyclic GMP.

Analysis of Saccharomyces cerevisiae genome revealed no sequence homologous to cyclic GMP (cGMP) dependent protein kinase from other organisms. Here we demonstrate that cyclic AMP (cAMP) dependent protein kinase purified from S. cerevisiae was almost equally activated by cAMP and cGMP in 3 x 10(-6) M concentrations of either nucleotide in the presence of Mg2+ ions. Interestingly, if Mn2+ ions were used instead of Mg2+, cGMP was only 30% as effective as cAMP in the activation of cAMP-dependent protein kinase. Analogs of cAMP such as 8-chloro-cAMP and 3':5'-cyclic monophosphate of ribofuranosylbenzimidazole were as potent as cAMP in the enzyme activation, while N6,2'-O-dibutyryl-cAMP activated the enzyme to a lower extent. It was also found that yeast cAMP-dependent protein kinase can be activated by limited proteolytic digestion. The results presented were obtained with protamine and ribosomal protein S10 used as phosphorylation substrates.

Cyclic AMP↗
PubMed2002

Structural analysis of fertilin(beta) cyclic peptide mimics that are ligands for alpha6beta1 integrin.

The NMR structural analysis of two fertilin(beta) mimics cyclo(EC2DC1)YNH2, 1, and cyclo(D2EC2D1C1)YNH2, 2 is described. Both of these mimics are moderate inhibitors of sperm-egg binding with IC50 values of 500 microm in a mouse in vitro fertilization assay. For peptide 1, the optimized conformations that best match the NMR data have a pseudo-type II' beta-turn with the linker and Glu at the i+1 and i+2 positions, respectively. The EC2D1C1 sequence is in a nonclassical (type IV) beta-turn. For peptide 2, the conformation that best matches the NMR data has two turns: a pseudo-type II' beta-turn in the D2EC2D1 sequence followed by a nonclassical beta-turn in the EC2D1C1 sequence. The Cbeta-Cbeta distance between E and D1 in peptide 1 is 9.1 A, in peptide 2, it is 7.7 A. Thus, one possibility for the high IC50 values of these cyclic peptides is that the acidic residues are not constrained to a sufficiently tight turn, and thus much entropy must still be lost upon binding to the alpha6beta1 integrin. This explains why the cyclic peptides are the same as linear peptides at inhibiting sperm-egg binding.

ADAM Proteins↗
PubMed1991

Phosphodiesterase II, the cGMP-activatable cyclic nucleotide phosphodiesterase, regulates cyclic AMP metabolism in PC12 cells.

Analysis of cyclic nucleotide phosphodiesterase (PDE) activity in cellular fractions from cultured rat pheochromocytoma (PC12) cells has shown that the predominant hydrolytic activity in both cytosolic and particulate compartments is characteristic of a PDE II, the cGMP-activatable family of PDE isozymes. Cytosolic PDE activity was purified to a high degree utilizing DE-52 anion exchange and cGMP-Sepharose affinity chromatographies. The physicochemical properties of PC12 PDE II were similar to those of PDE II isolated from particulate or soluble fractions of other tissues, including subunit molecular weight of approximately 102,000, activation of cAMP hydrolysis by cGMP, and positive cooperative kinetic behavior for cAMP and cGMP hydrolysis. The potential role of PDE II in regulating cAMP metabolism in intact PC12 cells was studied using an [3H]adenine prelabeling technique. Stimulation of PC12 cell adenosine receptors resulted in a 5-8-fold increase in cAMP accumulation. Removal of the adenosine stimulus by the addition of exogenous adenosine deaminase resulted in a rapid decay of cAMP to prestimulated basal levels within 2 min. Treatment of PC12 cells with atrial natriuretic factor or sodium nitroprusside caused 1) increased intracellular cGMP levels, 2) attenuation of adenosine-stimulated cAMP accumulation, and 3) increased rates of cAMP decay after removal of the adenosine stimulus. Treatment of PC12 cells with HL-725 (a potent inhibitor of isolated PDE II activity in vitro) caused 1) increased basal cAMP accumulation, 2) potentiation of adenosine-stimulated cAMP accumulation, and 3) retardation of the rate of cAMP decay after removal of the adenosine stimulus. HL-725 blocked both the attenuation of cAMP accumulation and the accelerated rate of cAMP decay observed with the cGMP-elevating agents. These results suggest that, in PC12 cells, drugs or hormones that inhibit PDE II or increase intracellular cGMP levels to activate PDE II can modulate cAMP metabolism by altering the catalytic status of the enzyme.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2006

Frequency analysis of air and skin temperature in neonates in servo-controlled incubators.

OBJECTIVE: To test a new system designed for digital recording of skin and air temperature, thereby allowing analysis of cyclic changes in temperature in neonates in servo-controlled incubators. METHODS: Analysis of cyclic changes of serial skin and air temperature in asymptomatic infants in servo-controlled incubators adjusting heat output to the patient's temperature. RESULTS: In nine asymptomatic neonates ranging from 25 to 40 weeks of gestational age, analysis showed peaks of coherence (squared correlation) between skin and air temperature measurements at periods ranging between 1.5 and 3 h. CONCLUSION: We have established a new system to study cyclic changes in skin and air temperature in neonates in servo-controlled incubators. The analysis of this pilot study suggests that the most important changes in skin and air temperature in asymptomatic neonates occur at a periodicity of 1.5 to 3 h, which is similar to that previously described for neonatal temperature. Additional data are required to determine whether this new system may be useful in neonatal care.

Air Conditioning↗
PubMed2003

Heart rate variability in obstructive sleep apnea: a prospective study and frequency domain analysis.

BACKGROUND: Cyclic variation of the heart rate is observed during apneic spells in obstructive sleep apnea (OSA). We hypothesized that autonomic changes would affect frequency-domain measures of heart rate variability (HRV). METHODS: We studied 20 patients (15 men, 5 women, mean age 47.2 +/- 12.2 years) with suspected OSA undergoing overnight polysomnography, and five patients (4 men, 1 woman, mean age 49.2 +/- 8.6 years) with recently diagnosed sleep apnea undergoing polysomnography while wearing continuous positive airway pressure (CPAP). Holter monitors were applied during sleep studies and data were analyzed in 5-minute blocks over the course of the night. Using spectral analysis, low frequency (LF) and high frequency (HF) powers were calculated for each interval. Overall mean and standard deviation (SD) for LF power, HF power, and the LF:HF ratio were recorded for each patient. Comparisons were made between patients with severe OSA (apnea hypopnea index (AHI) > 30, n = 8), moderate OSA (AHI 1-30, n = 5), without OSA (AHI < 10, n = 7), and patients wearing CPAP (n = 5). RESULTS: Assessment of overnight LF or HF power revealed no significant difference between the four groups. The LF:HF ratio, which represents sympathovagal balance, was higher among those with moderate disease compared to normals and those with severe OSA (both P = 0.037). The standard deviation of the LF:HF ratio was higher among those with moderate disease compared to normals (P = 0.0064) and those with severe OSA (P = 0.0006). OSA patients receiving CPAP behaved like patients with moderate OSA, with increased SD of the LF:HF ratio. CONCLUSIONS: The observed changes in the LF:HF ratio and its SD suggest an increased sympathetic tone and discordance in sympathovagal activity in moderate OSA, which is blunted in severe OSA. CPAP may restore autonomic defects, characteristic of severe OSA, to moderate levels.

Adult↗
PubMed2004

Evaluation and comparison of tailor-made stationary phases based on spherical silica-based beads for capillary electrochromatography via peptide separation analysis.

Small cyclic peptides have been employed to elucidate the performance of novel sorbents as stationary phases in capillary electrochromatography (CEC). In this paper chain length dependencies for ordinary liquid chromatographic sorbents are reported together with findings acquired on beads specifically designed to suit CEC. The latter, tailor-made, spherical, porous silica exhibits a distinguished surface modification to meet the criteria anticipated to enhance performance profiles in CEC. With well-characterised peptides resembling the analytes, probing of the CEC system in a systematic manner (predominantly via the organic modifier content of the background electrolyte (BE)) reveals insight into the complex interplay occurring in such analytical systems at the molecular and sub-molecular level in particular upon various modes of interaction.

Amino Acid Sequence↗
PubMed1983

Operant regulation of feeding: a static analysis.

Cyclic-ratio schedules are a rapid method for studying the operant regulation of feeding rate. The cyclic method produces results comparable to traditional but time-consuming parametric methods. Performance on cyclic-ratio schedules is well described by a linear regulatory model that embodies three quantitative feedback assumptions: (a) that rate of feeding is regulated by the rate of operant behavior, (b) that taste factors have an additive effect on the rate of the operant response, and (c) that regulatory "gain" is inversely related to body weight. This model accurately describes poorer regulatory performance at high body weights and following amphetamine administration, and the effects of altered diet palatability on preferred feeding rates.

Animals↗
PubMed1983

On the interactions of adenosine 3',5'-monophosphate with the components of protein kinase I. A theoretical equilibrium analysis.

Cyclic-AMP-dependent protein kinase is activated through the dissociation of active catalytic subunits from a regulatory dimer. The regulatory subunit consists of four cyclic-AMP-binding sites and two binding sites for catalytic subunits. Under well defined experimental conditions, protein kinase activation obeys apparent positive cooperativity and is linearly coupled to cyclic AMP binding. The simulation of theoretical models is used for testing working hypotheses. Here we demonstrate that the proposed stoichiometry of protein kinase activation may account for the experimentally observed properties of the system. The restrictive conditions under which theory and experimental observations are compatible are: (1) functional dependence between the two monomers of the regulatory dimer, (2) the only complexes which can accumulate at equilibrium in the considered conditions are R2C2, (cyclic AMP)2R2C and (cyclic AMP)4R2 (where R and C are the regulatory and catalytic subunits of protein kinase). An experimental procedure is proposed in order to check the validity of the theoretical predictions. The determination of the sequence of events leading to activation or inactivation of protein kinase is discussed.

Allosteric Site↗
PubMed1996

Cyclic HIV protease inhibitors: synthesis, conformational analysis, P2/P2' structure-activity relationship, and molecular recognition of cyclic ureas.

High-resolution X-ray structures of the complexes of HIV-1 protease (HIV-1PR) with peptidomimetic inhibitors reveal the presence of a structural water molecule which is hydrogen bonded to both the mobile flaps of the enzyme and the two carbonyls flanking the transition-state mimic of the inhibitors. Using the structure-activity relationships of C2-symmetric diol inhibitors, computed-aided drug design tools, and first principles, we designed and synthesized a novel class of cyclic ureas that incorporates this structural water and preorganizes the side chain residues into optimum binding conformations. Conformational analysis suggested a preference for pseudodiaxial benzylic and pseudodiequatorial hydroxyl substituents and an enantiomeric preference for the RSSR stereochemistry. The X-ray and solution NMR structure of the complex of HIV-1PR and one such cyclic urea, DMP323, confirmed the displacement of the structural water. Additionally, the bound and "unbound" (small-molecule X-ray) ligands have similar conformations. The high degree of preorganization, the complementarity, and the entropic gain of water displacement are proposed to explain the high affinity of these small molecules for the enzyme. The small size probably contributes to the observed good oral bioavailability in animals. Extensive structure-based optimization of the side chains that fill the S2 and S2' pockets of the enzyme resulted in DMP323, which was studied in phase I clinical trials but found to suffer from variable pharmacokinetics in man. This report details the synthesis, conformational analysis, structure-activity relationships, and molecular recognition of this series of C2-symmetry HIV-1PR inhibitors. An initial series of cyclic ureas containing nonsymmetric P2/P2' is also discussed.

Animals↗
PubMed2006

Combining impedance spectroscopy with cyclic voltammetry: measurement and analysis of kinetic parameters for faradaic and nonfaradaic reactions on thin-film gold.

The technique of time-resolved impedance spectroscopy can be combined with dc cyclic voltammetry (CV) to study mechanisms and kinetics of electrochemical reactions at solid-liquid interfaces. Utilization of these techniques in a combined framework, however, is based on a number of specific considerations of measurement procedures and data analysis. The present work discusses certain essential elements of this topic, focusing primarily on the analysis of time-resolved impedance spectra where interdependent dc and ac effects of parallel faradaic and nonfaradaic reactions are present under potentiodynamic conditions. A thin gold film is used as a model experimental system where oxidation and reduction of the sample surface is voltage-controlled both in the presence and in the absence of specifically adsorbing Cl- ions in neutral background electrolytes of NaF. Impedance spectra are recorded under transient conditions of CV, and kinetic parameters based on electrode-equivalent circuit models are obtained as functions of CV scans.

Gold↗