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Biomedical subjects

N Zhou

Publications and source records attributed to N Zhou.

65 records · Page 4Linked to original sources
PubMed1992

Developmental changes in the effects of drugs acting at NMDA or non-NMDA receptors on synaptic transmission in the chick cochlear nucleus (nuc. magnocellularis).

The developmental pharmacology of excitatory amino acid (EAA) receptors in the chick cochlear nucleus (nucleus magnocellularis, NM) was studied by means of bath application of drugs and recording of synaptically-evoked field potentials in brain slices taken from chicks aged embryonic day (E) 14 through hatching (E21). The abilities of various EAA agonists (N-methyl-D-aspartate [NMDA], kainic acid, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA]) to suppress postsynaptic responses by depolarization block and of EAA antagonists ((3-[RS]-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid [CCP], dizocilpine [MK-801], 6-nitro-7-sulfamoyl-benzo(F)quinoxaline-2,3 dione [NBQX], 6-cyano-7-nitroquinoxaline-2,3-dione [CNQX] and 6,7-dinitroquinoxaline-2,3-dione [DNQX]) to suppress these responses directly were assessed quantitatively. The results support the existence of NMDA receptors in NM and suggest that the ability of these receptors to influence synaptically-evoked responses declines dramatically during the last week of embryonic life. The results similarly suggest that the non-NMDA receptors in NM undergo changes in density and/or function during a period of development when the cochlear nucleus is undergoing a variety of morphological and functional transformations.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

Gamma-D-glutamylaminomethyl sulfonic acid (GAMS) distinguishes subtypes of glutamate receptor in the chick cochlear nucleus (nuc. magnocellularis).

Because kainic acid (KA) is more potent than other excitatory amino acids (EAAs) in affecting synaptic transmission in the cochlear nucleus, previous reports have concluded that primary afferent neurotransmission to the cochlear nucleus in birds and mammals is mediated by KA-preferring non-N-methyl-D-aspartate (non-NMDA) EAA receptors. Since this conclusion is at odds with a number of studies suggesting that rapid excitatory neurotransmission in the CNS is mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-preferring non-NMDA receptors, we re-examined the pharmacology of synaptic transmission between the cochlear nerve and nucleus magnocellularis (NM) in chickens, using bath application of drugs and recording of field potentials evoked in NM by electrical stimulation of the cochlear nerve in vitro. A series of EAA agonists produced complete, concentration-dependent and reversible suppression of postsynaptic responses: the order of potency was domoic acid (DO) greater than KA greater than AMPA much greater than quisqualic acid much greater than L-glutamic acid (Glu). Three quinoxalinedione antagonists of non-6-nitro-7-sulphamobenzo[f]quinoxaline-2,3-dione NMDA receptors also produced complete, concentration-dependent and reversible suppression of postsynaptic responses in NM without affecting the presynaptic action potential; the half-maximal inhibitory concentrations (IC50's) were 2.7 +/- 0.4 microM for 6-nitro-7-sulphamobenzo[f]quinoxaline-2,3-dione (NBQX), 5.3 +/- 0.1 microM for 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and 10.6 +/- 1.2 microM for 6,7-dinitroquinoxaline-2,3-dione (DNQX).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Proton NMR studies of angiotensin II and its analogs in aqueous solution.

The 1H nuclear magnetic resonance (NMR) spectra of angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) and five of its octapeptide analogs as well as angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) and angiotensin III (Arg-Val-Tyr-Ile-His-Pro-Phe) in aqueous solutions (90% H2O/10% D2O) were completely assigned by two-dimensional COSY and ROESY experiments. All of the peptides give rise to two distinct sets of signals. The minor set accounts for about 5% of the total population below pH 5.5 and increases to 12-20% around pH 7.0. The two sets of signals result from a cis-trans isomerization of the His-Pro peptide bond with the major resonances arising from the trans isomer. One analog in which the Pro is replaced with a D-Pro displays a very different isomerization behavior. The measured coupling constants JNH-alpha CH, the temperature dependence of the amide proton shifts and the relative intensities of the intraresidue and sequential NH-alpha CH ROEs, are all indicative of an extended backbone conformation for ANGII. However, some evidence for the existence of conformers with local structure involving preferred sidechain positions for the Tyr, His, Phe, and the carboxyl group of the Phe was found, particularly in the ROESY and pH-titration experiments. Moreover, pH effects and the unusual amide exchange behavior of the Arg epsilon NH suggests the presence of interactions between the Asp and Arg sidechains of ANGII. At low temperatures the Arg guanidinium NH2 protons were detected as two broad peaks which are related by sizeable exchange peaks in ROESY experiments. This behavior could be useful as a general probe for the study of Arg sidechain mobility and accessibility in other peptides and proteins.

Amino Acid Sequence↗
PubMed1991

Pharmacology of excitatory amino acid neurotransmission in nucleus laminaris of the chick.

The receptors mediating excitatory neurotransmission from the cochlear nucleus (nuc. magnocellularis, NM) to third-order auditory neurons in nucleus laminaris (NL) of the chicken were studied using in vitro brain slices, bath application of drugs, and electrophysiological recording of postsynaptic field potentials. Postsynaptic responses in NL were blocked completely, in a concentration-dependent and reversible fashion, by bath application of the broad-spectrum excitatory amino acid (EAA) antagonist kynurenic acid, the 'non-NMDA' EAA receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), and the EAA agonists domoic acid, kainic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and quisqualic acid. The selective NMDA receptor antagonists 3-[-)-2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP) and dibenzocycloheptenimine (MK-801) had no effect. The results demonstrate that excitatory input from the cochlear nucleus to NL is mediated by non-NMDA (G2) EAA receptors which exhibit some of the pharmacologic features typical of the AMPA receptors defined by binding studies.

Amino Acids↗
PubMed1989

Binding of actinomycin D to [d(ATCGAT)]2: NMR evidence of multiple complexes.

Actinomycin D (actD) binds to the oligonucleotide [d(ATCGAT)]2 with a hypochromatic and red-shifted visible absorbance band compared to free drug and a CD spectrum with double negative bands at 460 and 385 nm. These spectral features are similar to those of the actD-[d(ATGCAT)]2 complex, while actD-[d(AT)5]2 gives spectra similar to those of free drug. Upon dilution or raising the temperature, the spectral characteristics accompanying complex formation disappear in the actD-[(ATCGAT)]2 sample but remain in the actD-[d(ATGCAT)]2 complex under the same experimental conditions. These results suggest that (a) sequence-specific binding of actD occurs with [d(ATCGAT)]2 but not with [d(AT)5]2, (b) the binding is not as strong as with [d(ATGCAT)]2, and (c) actD binds [d(ATCGAT)]2 with the same mechanism as it binds [d(ATGCAT)]2, i.e., by intercalation. From NMR spectra of the actD-[d(ATCGAT)]2 complex, three types of signals can be detected below 20 degrees C, one major and two minor ones. At higher temperatures, exchange between the two minor ones becomes fast enough that only one type of minor signal was seen. Partial resonance assignments were made by using 2D nuclear Overhauser effect (NOE) and 2D homonuclear Hartmann-Hahn (HOHAHA) experiments. Proton chemical shift changes of the major complex are consistent with actD chromophore ring intercalation between hexamer base pairs. Data from NOE-detected dipolar interactions between actD and [d(ATCGAT)]2 protons were interpreted in terms of a major complex with the actD chromophore ring system intercalated at the CG position and minor complexes with the drug intercalated off center at the GA positions.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1989

Virion proteins of viruses causing hemorrhagic fever with renal syndrome; monoclonal antibody analysis.

SDS-polyacrylamide gel electrophoresis and Western blotting analysis by using 9 clones of monoclonal antibodies specific for hemorrhagic fever with renal syndrome (HFRS) viruses were carried out on the virion proteins of 17 strains of HFRS viruses isolated from different areas in Asia and different hosts such as Apodemus agrarius, Rattus norvegicus, domestic cat and HFRS patients. Polypeptide with apparent molecular weight about 50 kitodalton (Kd) could be detected in all 17 strains of HFRS viruses. On this polypeptide there are two different antigenic determinants and one of them might be genus specific.

Animals↗
PubMed1988

Deoxyribose ring conformation of [d(GGTATACC)]2: an analysis of vicinal proton-proton coupling constants from two-dimensional proton nuclear magnetic resonance.

Exchangeable and nonexchangeable protons of [d(GGTATACC)]2 in aqueous cacodylate solution were assigned from two-dimensional nuclear Overhausser effect (2D NOE) spectra. With phase-sensitive COSY and double quantum filtered COSY (DQF-COSY) experiments, the cross-peaks resulting from deoxyribose ring conformation sensitive proton-proton vicinal couplings, i.e., all 1'-2', 1'-2", 2'-3', and 3'-4' couplings and six from 2"-3' couplings, were observed. From the cross-peak fine structure, the 2',2" proton assignments can be confirmed; coupling constants J1'2' and J1'2" and sums of coupling constants involving H2' and H2" for all residues and H3' for C8 were obtained. The DISCO procedure [Kessler, H., Muller, A., & Oschkinat, H. (1985) Magn. Reson. Chem. 23, 844-852] was used to extract individual 1'-2' and 1'-2" coupling constants. The sum of coupling constants involving H1' or H3' was measured from the one-dimensional spectrum where signal overlap is not a problem. Analysis of the resulting coupling constants and sums of coupling constants, in the manner of Rinkel and Altona [Rinkel, L. J., & Altona, C. (1987) J. Biomol. Struct. Dyn. 4, 621-649], led to the following conclusion: C2'-endo deoxyribose ring conformation is predominant for every residue, but a significant amount of C3'-endo conformation may exist, ranging from 14% to 30%.

Carbohydrate Conformation↗
PubMed1987

Solution structure of [d(GGTATACC)]2: wrinkled D structure of the TATA moiety.

Phase-sensitive two-dimensional nuclear Overhauser effect spectra of [d(GGTATACC)]2 in aqueous deuterium oxide solution at four mixing times were quantified to give all nonoverlapping cross-peak intensities. A structural model for [d(GGTATACC)]2 was built in which the GG- and -CC moieties were in the B-DNA form, while the middle -TATA- moiety was in the wrinkled-D form (BDB model). This model was subjected to energy refinement by molecular mechanics calculations with the program AMBER. Counterions (Na+) were added to neutralize the charges, and water molecules were placed bridging across the minor groove. A complete relaxation matrix analysis was used to calculate two-dimensional nuclear Overhauser effect spectra of [d(GGTATACC)]2 from the above models (before and after energy refinement) and from four other [d(GGTATACC)]2 structural models: regular A, crystalline A, regular B, and energy-minimized B. Among them, the energy-minimized BDB model yielded a set of theoretical spectra that gave the best fit to the experimental spectra. It was also the energetically most stable. Therefore, it is a good representation of the ensemble- and time-averaged structure of the octamer in solution. This model has backbone torsion angles similar to those of B-form DNA in the GG- and -CC moieties and torsion angles similar to those of wrinkled D form DNA in the -TATA- moiety. The base stacking and base pairing are not interrupted at the junctions between the two structural moieties. Its minor groove is narrower than that of B DNA, and the solvent-accessible surface of the minor groove forms a closed hydration tunnel in the middle -TATA- segment.

Adenine↗
PubMed1983

Etiologic studies of epidemic hemorrhagic fever (hemorrhagic fever with renal syndrome).

Two strains of epidemic hemorrhagic fever (EHF) virus were isolated from the lung tissues of Apodemus agrarius mice that were captured in an area where EHF is endemic. The strains were isolated by passages in A. agrarius mice from a nonendemic area. Identification of the isolates by usual procedures was confirmed by repeated blind tests with coded sera. Contamination with certain known viruses such as reovirus, adenovirus (types 3 and 7), and other pathogens, such as murine typhus rickettsiae and Leptospira, which may be naturally present in wild rodents, appeared to have been ruled out. The antigen slides made from these isolates are in use in the specific diagnosis and seroepidemiologic studies of EHF. The first successful application is the serodiagnosis of a mild type of hemorrhagic fever that occurs with characteristic epidemiologic features in certain provinces of China.

Animals↗
PubMedDate not supplied

1H-NMR studies of [Sar1]angiotensin II conformation by nuclear Overhauser effect spectroscopy in the rotating frame (ROESY): clustering of the aromatic rings in dimethylsulfoxide.

The conformational properties of the octapeptide [Sar1]ANG II in dimethylsulfoxide-d6 were investigated by rotating frame nuclear Overhauser effect spectroscopy (ROESY). Interresidue ROESY interactions were observed between Tyr ortho and Phe ring protons, between Phe ring and Pro C gamma protons, and also between His C alpha and Pro C delta protons. A weak connectivity was also observed between the Sar N-CH3 protons and a Tyr ortho proton. Intraresidue interactions between alpha and beta protons in Tyr, His and Phe indicated restricted rotation for the side-chains of the three aromatic residues. These findings suggest that [Sar1]ANG II takes up a folded conformation in DMSO in which the three aromatic rings form a cluster. Connectivities between the His C alpha proton and the two Pro C delta protons illustrated a preferred conformation for angiotensin II in DMSO in which the His-Pro bond exists as the trans isomer. The NMR spectroscopic evidence is consistent with the presence of a Tyr charge relay system in the biologically active conformation of angiotensin II and with the postulated role of the Tyr hydroxyl group in angiotensin II for receptor activation.

Amino Acid Sequence↗