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61.
The effect of GABA on in vitro binding of two novel non-benzodiazepines, PK 8165 and CGS 8216, to benzodiazepine receptors in the rat brain 总被引:1,自引:0,他引:1
The effect of gamma-aminobutyric acid (GABA) on the binding of PK 8165, a quinoline derivative, and CGS 8216, a pyrazoloquinoline, was assessed in two different regions of the rat brain. PK 8165, a compound with reported anxiolytic properties, inhibited [3H]-propyl beta-carboline-3-carboxylate labeled receptors in the cerebellum with an IC50 of 844 nM and 370 nM in the absence and presence of micro M GABA, respectively. GABA (100 micro M) was less effective in the cerebral cortex, decreasing the IC50 value from 280 to 197 nM. In saturation isotherm studies with [3H]-CGS 8216, a benzodiazepine receptor antagonist, GABA (100 micro M) induced a small but significant reduction in the apparent affinity of [3H]-CGS 8216 for benzodiazepine receptors in the cerebral cortex but the Bmax was unchanged. 相似文献
62.
Precise and quantitative reversed-phase high performance liquid chromatographic (HPLC) procedures are described which can be used in biogenic amine and neuropeptide research. The amine procedure was applied to various pharmacological matrices including plasma, heart tissue and brain. The use of peptide HPLC as an analytical tool for various neuropeptides is illustrated by studies on des-tyrosine-gamma-endorphin (DT gamma E) metabolism in the brain and the stability of an ACTH (ORG-2766) analogue during a chronic infusion in rats. The power of HPLC as a research tool in peptide pharmacology is described, discussed and demonstrated as an aid in the understanding of the pharmacological effects of exogenous peptides and the function of the brain. 相似文献
63.
The novel pyrazoloquinoline, CGS, 9896, was a potent inhibitor of specific [3H]-flunitrazepam binding in several brain regions with subnanomolar KI values. The inhibition of [3H] propyl beta-carboline-3-carboxylate ([3H]-PCC-) binding by CGS 9896 was enhanced by gamma-aminobutyric acid (GABA) but not by chloride ion. GABA enhancement of CGS 9896 inhibition of [3H]-PCC binding predicts this compound has benzodiazepine (BZD) agonist-type activity. Behavioral studies support this prediction. CGS 9896 was found to protect mice against bicuculline and metrazol induced seizure at doses that did not induce ataxia or sedation. CGS 9896 may represent a class of compounds with potential therapeutic value. The high affinity of this non-BZD compound suggests that CGS 9896 may also be of value as a high affinity ligand for the continued study of BZD receptors. 相似文献
64.
Nitrobacter agilis cytochrome c-550 was purified to an electrophoreticallyhomogeneous state, and some of its properties were determined.The cytochrome showed an absorption peak at 410 nm in the oxidizedform, and peaks at 416, 521 and 550 nm in the reduced form.Its isoelectric point was 8.1 at 5?C. Analysis of the aminoacid composition showed that the cytochrome molecule was composedof 108 amino acid residues, 16 of which were lysine residues. The cytochrome reacted rapidly with N. agilis cytochrome c oxidaseand yeast cytochrome c peroxidase and more slowly with Pseudomonasaeruginosa nitrite reductase and bovine cytochrome c oxidase.The reactivities with these redox enzymes suggested that thecytochrome might be an evolutionary stage between bacterialand eukaryotic cytochromes c. The primary structure of the cytochrome from the N-terminusto the 85th residue was determined. The N-terminal sequencewas homologous to the corresponding portion of the primary structureof horse cytochrome c.
1 Present adress: Department of Chemistry, Faculty of Science,Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo,152, Japan. (Received December 3, 1981; Accepted January 28, 1982) 相似文献
65.
Induction of proliferation and Ig production in human B leukemic cells by anti-immunoglobulins and T cell factors 总被引:20,自引:0,他引:20
K Yoshizaki T Nakagawa T Kaieda A Muraguchi Y Yamamura T Kishimoto 《Journal of immunology (Baltimore, Md. : 1950)》1982,128(3):1296-1301
The proliferation and differentiation of human leukemic B cells (B-CLL cells) with anti-Ig and T cell-derived helper factors are described. Stimulation of B-CLL cells with anti-Ig and T helper factors could induce proliferation as well as differentiation into IgM- and IgG-producing cells. Neither anti-Ig nor T helper factors alone could induce any proliferation and/or differentiation of B-CLL cells. Not only whole molecules of anti-Ig but also F(ab')2 fragments could induce proliferation and differentiation of B-CLL cells in the presence of T helper factors, but monovalent Fab' fragments were not effective. Induction of both IgM and IgG with the same idiotype was confirmed by immunofluorescent and SDS-PAGE analysis. By employing an IL 2-dependent cytotoxic T cell line and a TRF-responsive B cell line, T cell factors were separated into a fraction with IL2 activity but no TRF activity and a fraction with TRF activity but no IL 2 activity by chromatofocusing. Anti-Ig and IL 2 fraction could induce proliferation of B-CLL cells, but TRF fraction was not effective for the induction of proliferation in anti-IG-stimulated cells. For IgM and IgG production, anti-Ig and both IL 2 and TRF fractions were required. Depletion of IL 2 fraction in the first 2 days' culture inhibited Ig production, whereas the absence of TRF fraction in the first 2 days did not show any inhibitory effect on Ig production. 相似文献
66.
Y Morimoto T Oishi N Hanasaki A Miyatake K Noma Y Yamamura 《Endocrinologia japonica》1980,27(5):659-666
The relative potency in the hypothalamic-pituitary-adrenal (HPA) suppression of both prednisolone and betamethasone was examined in an acute study with normal volunteers and in a chronic study with glucocorticoid-treated patients. Circadian rhythm of plasma cortisol was studied after a single dose administration of 5 to 30 mg prednisolone or 0.5 to 3.0 mg betamethasone at 8:00 hr. Morning-rise of plasma cortisol occurred on the morning after the administration of 30 mg or less prednisolone but no morning rise was noted after the administration of 1.0 mg or more betamethasone. Plasma ACTH was slightly elevated on the morning after 30 mg prednisolone administration but showed low levels throughout the night after 3.0 mg betamethasone administration. Plasma cortisol responsiveness to ACTH was examined in patients before and during therapy with either prednisolone or betamethasone. The basal cortisol level was not suppressed and the responsiveness to ACTH remained nearly normal during long-term 5 mg prednisolone therapy, but these were completely suppressed during long-term 5 mg betamethasone therapy. The responsiveness to ACTH was nearly normal in patients receiving alternate-day therapy with prednisolone in such large doses as 50 or 60 mg every other day, but was completely suppressed in patients receiving 1.0 mg betamethasone every other day. The relative potency of betamethasone in acute and chronic suppressive effects on the HPA system seems to be much stronger than that of prednisolone in equivalent doses with comparable anti-inflammatory effects. It is also suggested that the alternate-day therapy with such long-acting steroids as betamethasone are useless in preventing HPA suppression. 相似文献
67.
68.
Cardiac muscarinic cholinergic receptors. Biochemical identification and characterization 总被引:25,自引:0,他引:25
J Z Fields W R Roeske E Morkin H I Yamamura 《The Journal of biological chemistry》1978,253(9):3251-3258
69.
M Okada T Kishimoto T Igarashi T Teranishi Y Yamamura 《Journal of immunology (Baltimore, Md. : 1950)》1978,120(4):1097-1101
The macrophage tumor cell line J774.1 replaced the function of normal macrophages in the induction of polyclonal killer T cells with 2-mercaptoethanol. J774.1 does not normally release soluble factor(s) which we have shown to be responsible for the differentiation of T cells to killer T cells. However, stimulation of J774.1 with LPS induced soluble factor(s) for T cell activation. An optimum concentration of LPS for the production of soluble factor(s) was 1 to 10 microgram/ml, which completely inhibited growth of the tumor cells. The production of soluble factor(s) was observed within 6 hr after LPS stimulation and reached its maximum level at 24 hr. Incubation of the cell line with 8Br-cyclic AMP and theophylline induced soluble factor(s), suggesting that LPS stimulation induced an increase in intracellular cyclic AMP which leads to the synthesis of soluble factor(s). 相似文献
70.
The effect of temperature on CL 218872 and propyl beta-carboline-3-carboxylate inhibition of [3H]-flunitrazepam binding in rat brain 总被引:1,自引:0,他引:1
K W Gee M Morelli H I Yamamura 《Biochemical and biophysical research communications》1982,105(4):1532-1537
The competitive inhibition of [3H]-flunitrazepam binding by CL 218872 and propyl beta-carboline-3-carboxylate (PCC), non-benzodiazepine compounds that show differential affinities for benzodiazepine (BZD) receptor subtypes, was studied in the rat cerebral cortex and hippocampus at different temperatures of incubation. The potency of both inhibitors was significantly greater at 0° than at 37°C. The magnitude of temperature induced enhancement of potency may correlate with the pharmacological efficacy of compounds that interact with BZD receptors. Hill slopes for CL 218872 shifted from 0.52 to 0.97 in the cerebral cortex when incubations were performed at 0° and 37°C, respectively. Hill values for PCC changed from 0.68 to 0.93 under similar temperature conditions. These observations suggest the presence of a homogenous population of benzodiazepine receptors at physiological temperatures or the inability of CL 218872 and PCC to distinguish between receptor subtypes at 37°C. 相似文献