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101.
Allosteric Modulation of Flunitrazepam Binding to Rat Brain Benzodiazepine Receptors by Methyl β-Carboline-3-Carboxylate 总被引:4,自引:3,他引:1
The inhibition of flunitrazepam (FNP) binding to rat brain benzodiazepine (BZ) receptors by methyl beta-carboline-3-carboxylate (MCC) was studied. Biphasic dissociation was observed for [3H]FNP and [3H]MCC in cerebral cortex, cerebellum, and hippocampus, although the dissociation of [3H]MCC was much faster. The dissociation rate of [3H]FNP was increased by MCC in the cerebellum, but was not altered in cerebral cortex or hippocampus. [3H]FNP binding stimulated by gamma-aminobutyric acid was enhanced in the presence of MCC in all three regions examined. These results indicate that MCC exerts these effects by interacting with allosteric sites that are different from the FNP recognition sites on the BZ receptors. 相似文献
102.
103.
Cooper David N. Smith Barbara A. Cooke Howard J. Niemann Susanne Schmidtke Jörg 《Human genetics》1985,71(3):201-205
Summary Patients with recessive X-linked ichthyosis
Patients with recessive X-linked ichthyosis (RXLI), one hereditary form of scaly skin, lack activity of the enzyme steroid
sulfatase in all tissues studied. To investigate the molecular defect underlying the lack of enzyme activity, we prepared
antisera against normal enzyme by injecting normal placental microsomal suspensions or partially purified steroid sulfatase
into rabbits. Antibody activity was assessed by immunoprecipitation of detergent solubilized steroid sulfatase. In addition,
we prepared rabbit antisera against RXLI placental microsomal suspensions. To detect immunologically cross-reactive material
in patients' placentas, extracts were studied by immunoblot techniques and by competition with normal enzyme for antibody
binding. Patients' extracts did not contain immunoreactive material co-migrating on electrophoresis with purified enzyme nor
did they inhibit immunoprecipitation of normal enzyme. Sera from rabbits immunized with RXLI placental microsomes contain
no antibodies to normal steroid sulfatase, as judged by their failure to immunoprecipitate normal enzyme or to react with
normal steroid sulfatase on immunoblot. Thus the mutation in RXLI appears to reduce steroid sulfatase enzyme protein as well
as enzyme activity.
Portions of this material have appeared in abstract form in Clinical Research 31:564A, 1983 and 32:138A, 1984 相似文献
104.
Malaria parasites do not contain or synthesize sialic acids 总被引:1,自引:0,他引:1
R Schauer M Wember R J Howard 《Hoppe-Seyler's Zeitschrift für physiologische Chemie》1984,365(2):185-194
The capacity of Plasmodia to synthesize sialic acids was investigated by adding radioactive acetate to short-term in vitro cultures of the intraerythrocytic asexual forms of three malaria parasites (the human malaria Plasmodium falciparum in Aotus trivirgatus erythrocytes; the simian malaria P. knowlesi in rhesus monkey erythrocytes; the rodent malaria P. berghei in mouse erythrocytes) and to cultures of extracellular zygotes of the avian malaria P. gallinaceum. Radioactive acetate was added to normal rhesus monkey erythrocytes and to cells of the murine myeloma NS-1 for comparison. Although [1-14C]-acetate labeled many proteins with each malaria parasite and the NS-1 cells, analysis of purified sialic acids revealed that only with the NS-1 cells was radioactivity incorporated into sialic acids. Furthermore, N-acetyl[6-3H]mannosamine was not incorporated into sialic acids or malarial glycoproteins when added to P. knowlesi cultures. All of the malaria parasites underwent growth or differentiation during these experiments as measured by [35S]methionine uptake into protein and by light microscopy. Extracellular parasites largely free of erythrocyte membranes were prepared to determine whether Plasmodia contain sialic acids that are not labeled by exogenous precursors. Purified merozoites of P. knowlesi and zygotes of P. gallinaceum did not contain detectable amounts of sialic acids on chemical analysis. Thus, although we could show that Plasmodia can incorporate radioactive sugars such as glucosamine, galactose and mannose into proteins, presumably glycoproteins, they do not synthesize sialic acids or sialo-glycoproteins, nor do they contain sialo-glycoconjugates of host origin. 相似文献
105.
Edwin K. Jackson Howard D. Uderman William A. Herzer Robert A. Branch 《Life sciences》1984,35(2):221-228
The purpose of this study was to determine the effects of chronic administration of the thromboxane synthetase inhibitor, UK 38,485, on noradrenergic neurotransmission. Male Sprague Dawley rats (n=14) were treated once daily with either UK 38,485 (100 mg/kg; n=7) or the vehicle of UK 38,485 (olive oil; n=7) by gavage. The dose of UK 38,485 chosen was sufficient to inhibit platelet TXB2 production by >90% for 24 hours. One week into the treatment animals were prepared for perfusion of their mesenteric vascular beds. Vasoconstrictor responses to both exogenous norepinephrine and periarterial nerve stimulation were determined both before and during an infusion of angiotensin II (9ng/min) into the superior mesenteric artery. UK 38,485 significantly (P<0.02) attenuated the vascular response to periarterial nerve stimulation without altering the vascular response to either norepinephrine or angiotensin II. UK 38,485 did not influence the baseline perfusion pressure, the mean arterial blood pressure or the potentiation of neurotransmission by angiotensin II. These data indicate that in the rat mesentery UK 38,485 attenuates the release of neurotransmitter from sympathetic nerve terminals. 相似文献
106.
Lloyd A. Greene P. John Seeley Adriana Rukenstein Margaret DiPiazza rew Howard 《Journal of neurochemistry》1984,42(6):1728-1734
Abstract: Nerve growth factor protein (NGF) was found to rapidly promote the activation of tyrosine hydroxylase in cultured rat PC 12 pheochromocytoma cells. PC 12 cultures were exposed to NGF for periods of less than 1 h and the soluble contents of homogenates prepared from the cells were assayed for tyrosine hydroxylase activity. Under these conditions, the specific enzymatic activity was increased by 60 ± 10% (n = 13) in comparison with that in untreated sister cultures. The increase was half maximal by 2–5 min of exposure and at NGF concentrations of about 10 ng/ml (0.36 n M ). Antiserum against NGF blocked the effect. Tyrosine hydroxylase activity could also be rapidly increased by NGF in cultures of PC12 cells that had been treated with the factor for several weeks in order to produce a neuron-like phenotype. This was achieved by withdrawing NGF for about 4 h and then readding it for 30 min. The NGF-induced increase of tyrosine hydroxylase activity in PC12 cultures was not affected by inhibition of protein synthesis and therefore appeared to be due to activation of the enzyme. Kinetic experiments revealed that NGF brought about no change in the apparent Km of the enzyme for tyrosine or for co-factor (6-methyltetrahydropteridine), but that it did significantly increase the apparent maximum specific activity of the enzyme. These observations suggest that NGF (perhaps released by target organs) could promote a rapid and local enhancement of noradrenergic transmission in the sympathetic nervous system. 相似文献
107.
A G Diamond G W Butcher J C Howard 《Journal of immunology (Baltimore, Md. : 1950)》1984,132(3):1169-1175
We describe two monoclonal antibodies, R3/47 and YR1/1, directed against different epitopes of the expressed rat class I major transplantation antigen RT1Aa, that interact with each other so that the binding of one antibody, YR1/1, is greatly enhanced by the binding of the other. The positive interaction between R3/47 and YR1/1 also occurs when using RT1Aa molecules solubilized from cell membranes in detergent. It is therefore unlikely that the molecular environment of the membrane contributes to the interaction. The ability of R3/47 to modify the YR1/1 determinant on the RT1Aa molecule is mediated without any significant loss of potency by highly purified monomeric Fab fragments. This result suggests that the binding of R3/47 to the RT1Aa molecule alters the YR1/1 determinant by initiating a propagated conformational change in the antigen. 相似文献
108.
Blood was obtained from three species of macaques for a study of platelets. A rapidly mobilizable platelet pool was demonstrated in rhesus macaques given intravenous epinephrine. The number of platelets/ml of blood increased about 30% 3 to 5 min after epinephrine was given. The size distributions of the platelets were similar before and after injection. Platelet aggregability was increased after injection. Basal platelet aggregabilities, as measured by platelet aggregate ratios, were similar in rhesus macaques. Celebes black macaques, and human subjects, but were significantly greater in cynomolgus macaques than in the other three species. 相似文献
109.
Notexin belongs to a class of snake venom neurotoxins and myotoxins that have phospholipase A2 activity. Previous studies have shown that these toxins affect target cells differently from phospholipases that are not neurotoxic or myotoxic. Notexin inhibited the Ca2+ uptake into fragmented sarcoplasmic reticulum from rabbit skeletal muscle, but it did not cause an efflux of previously accumulated Ca2+ or inhibit the Ca2+--ATPase activity. It is suggested that notexin specifically binds to and decreases the conductance for Ca2+ of the Ca2+ pump and/or the conductance of a channel for an ion that facilitates Ca2+ transport. The K+ ionophore valinomycin reversed the notexin-induced inhibition of Ca2+ uptake into sarcoplasmic reticulum, suggesting that the molecular target of notexin could be a K+ channel. Two types of reconstitution experiments make it unlikely that notexin acts by degrading a minor lipid that is resistant to hydrolysis by nontoxic phospholipases A2. Notexin-inactivated sarcoplasmic reticulum vesicles were reactivated (with respect to Ca2+ uptake) by simple solubilization with detergent and subsequent reconstitution by detergent removal. Second, notexin was still active on sarcoplasmic reticulum vesicles after greater than 94% of the lipids were replaced by soybean phosphoglycerides during the reconstitution procedure. 相似文献
110.
Summary Anoxia has been shown to induce the expression of one or more stress proteins in mammalian cells and tissues. A less severe form of oxygen depletion, hypoxic hypoxia, occurs in response to hypobaric decompression which simulates high altitude conditions. Under these conditions mouse hearts accumulate mRNAs for at least two polypeptides at substantially elevated levels. The molecular weights of these proteins, 85 kDa and 95 kDa, are similar to those reported for other mammalian stress proteins or glucose-regulated proteins. Time course experiments suggest that mRNAs for these species increase continuously for up to 16 hours of treatment, while mRNA for 71 kDa and 79 kDa polypeptides are elevated early in the treatment, but later decrease to control values. Total heart mRNA template activity is also increased by the hypobaric treatment. These results demonstrate that mouse cardiac tissue is capable of mounting a cellular stress-like response when exposed to moderately stressful conditions. It also provides a model for studying the direct effects of acute hypoxic stress on cellular gene expression, and its relationship to physiological adaptation. 相似文献