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1.
Using enzymic digestion with pectinase, controlled Smith degradation and NMR-spectroscopy, some structural features of the hairy region of pectic polysaccharide termed silenan SV from the aerial part of campion Silene vulgaris (Moench) Garke ( Oberna behen (L.) Ikonn) were elucidated. Silenan was subjected to enzymic digestion with pectinase to furnish the polysaccharide fraction (SVP). The contained residues of
-galacturonic acid (43%), arabinose, galactose and rhamnose as main constituents. The backbone of the hairy region of silenan was found to consist of -1,4-galactopyranosyl uronic acid and 2-O-glycosylated rhamnopyranose residues. The side chains contained linear regions of residues of -1,5-linked arabinofuranose and β-1,3-, β-1,4-linked galactopyranose. Silenan SV and its fragment SVP were subjected to Smith degradation to give fractions SVS and SVPS. These contain the residues of terminal and 2-substituted -arabinofuranose as well as residues of terminal, 3-, and 2,3-substituted β-galactopyranose. In addition, NMR-spectral data confirmed that the residues of -rhamnopyranose 2-O-glycosylated with the residues of -1,4-galactopyranosyl uronic acid of the backbone occurred in the core of SVPS and, therefore, in the backbone of silenan SV. On the basis of data obtained, the hairy regions of silenan were suggested to contain mainly the linear chains of β-1,3-, β-1,4-galactopyranan and -1,5-arabinofuranan. The chains of -1,5-linked arabinofuranose, β-1,3- and β-1,4-linked galactopyranose were shown to be involved in the side chains of the hairy region having branching points at 2,3-substituted β-galactopyranose residues. 相似文献
2.
Recently, it has been shown that PKA-mediated phosphorylation of the β 2-adrenergic receptor (β 2-AR) by the cyclic AMP-dependent protein kinase (PKA) reduces its affinity for G s and increases its affinity for G i. Here we demonstrate that, like the β 2-AR, the β 1-AR is also capable of “switching” its coupling from G s to G i in a PKA-dependent manner. The β 1-AR is capable of activating adenylate cyclase via G s, and can also activate the extracellular-regulated kinases, p44 and p42 (ERK1/2). In transfected CHO cells, the observed β 1-AR-mediated activation of ERK is both sensitive to pertussis toxin (PTX), indicating involvement of G i/G o, and to the PKA inhibitor, H-89. β 1-ARs with PKA phosphorylation sites mutated to alanines are unable to activate ERK. Mutating these same residues to aspartic acid, mimicking PKA phosphorylation, leads to a decrease in G s-stimulated cAMP accumulation and an increase in PTX-sensitive ERK activation. These results strongly support the hypothesis that the β 1-AR, like the β 2-AR, can undergo PKA-dependent “G s/G i switching”. 相似文献
3.
It has been suggested that the F 1-ATPase β-subunit is the enterostatin receptor. We investigated the binding activity of the purified protein with a labeled antagonist, β-casomorphin 1–7, in the absence and presence of cold enterostatin. 125I-β-casomorphin 1–7 weakly binds to the rat F 1-ATPase β-subunit. Binding was promoted by low concentrations of cold enterostatin but displaced by higher concentrations. To study the relationship between binding activity and feeding behavior, we examined the ability of a number of enterostatin analogs to affect β-casomorphin 1–7 binding to the F 1-ATPase β-subunit. Peptides that suppressed food intake promoted β-casomorphin 1–7 binding whereas peptides that stimulated food intake or did not affect the food intake displaced β-casomorphin 1–7 binding. Surface plasmon resonance measurements show that the β-subunit of F 1-ATPase binds immobilized enterostatin with a dissociation constant of 150 nM, where no binding could be detected for the assembled F 1-ATPase complex. Western blot analysis showed the F 1-ATPase β-subunit was present on plasma and mitochondrial membranes of rat liver and amygdala. The data provides evidence that the F 1-ATPase β-subunit is the enterostatin receptor and suggests that enterostatin and β-casomorphin 1–7 bind to distinct sites on the protein. 相似文献
4.
The phosphinoalkenes Ph 2P(CH 2) nCH=CH 2 ( n= 1, 2, 3) and phosphinoalkynes Ph 2P(CH 2) n C≡CR (R = H, N = 2, 3; R = CH 3, N = 1) have been prepared and reacted with the dirhodium complex (η−C 5H 5) 2Rh 2(μ−CO) (μ−η 2−CF 3C 2CF 3). Six new complexes of the type (ν−C 5H 5) 2(Rh 2(CO) (μ−η 1:η 1−CF 3C 2CF 3)L, where L is a P-coordinated phosphinoalkene, or phosphinoalkyne have been isolated and fully characterized; the carbonyl and phosphine ligands are predominantly trans on the Rh---Rh bond, but there is spectroscopic evidence that a small amount of the cis-isomer is formed also. Treatment of the dirhodium-phosphinoalkene complexes with (η−CH 3C 5H 4)Mn(CO) 2thf resulted in coordination of the manganese to the alkene function. The Rh 2---Mn complex [(η−C 5H 5) 2Rh 2(CO) (μ−η 1:η 1−CF 3C 2CF 3) {Ph 2P(CH 2) 3CH=CH 2} (η−CH 3C 5H 4)Mn(CO) 2] was fully characterized. Simi treatment of the dirhodium-phosphinoalkyne complexes with Co 2(CO) 8 resulted in the coordination of Co 2(CO) 6 to the alkyne function. The Rh 2---Co 2 complex [(η−C 5H 5) 2Rh 2(CO) (μ−η 1:η 1−CF 3C 2CF 3) {Ph 2PCH 2C≡CCH 3}Co 2(CO) 2], C 37H 25Co 2F 6O 7PRh 2, was fully characteriz spectroscopically, and the molecular structure of this complex was determined by a single crystal X-ray diffraction study. It is triclinic, space group
( Ci1, No. 2) with a = 18.454(6), B = 11.418(3), C = 10.124(3) Å, = 112.16(2), β = 102.34(3), γ = 91.62(3)°, Z = 2. Conventional R on | F| was 0.052 fo observed ( I > 3σ( I)) reflections. The Rh 2 and Co 2 parts of the molecule are distinct, the carbonyl and phosphine are mutually trans on the Rh---Rh bond, and the orientations of the alkynes are parallel for Rh 2 and perpendicular for Co 2. Attempts to induce Rh 2Co 2 cluster formation were unsuccessful. 相似文献
5.
目的: 构建α 1亚基诱导表达、β 2和γ 2L亚基稳定表达的人源α 1β 2γ 2L-GABA AR-CHO(Chinese hamster ovary)细胞株。方法: 从人cDNA文库中扩增α 1、β 2、γ 2L亚基编码基因,分别构建亚基表达载体;将三个亚基表达载体共转染CHO-K1细胞,通过抗性筛选、膜电位检测法进行稳定表达克隆筛选;通过qPCR、Western blot对亚基表达进行鉴定;以激动剂GABA、阳性变构调节剂地西泮(diazepam,Dia)、拮抗剂荷包牡丹碱(bicuculine)为工具药,采用全细胞膜片钳方法及膜电位检测法对稳定表达细胞的药理学功能进行鉴定。结果: 经克隆筛选获得表达量较高的α 1β 2γ 2L-GABA AR-CHO并对其亚基表达鉴定,结果显示该细胞稳定表达α 1、β 2、γ 2L亚基,构建的α 1β 2γ 2L-GABA AR-CHO细胞仅在加入四环素(tetracyclin)诱导的情况下表达α 1亚基并与β 2、γ 2L组装成具有功能活性的α 1β 2γ 2L-GABA AR;对其进行全细胞膜片钳检测研究发现,GABA可对其产生激动效应,引起α 1β 2γ 2L-GABA AR-CHO细胞产生氯离子通道特征性电流变化,Dia可剂量依赖性地增强GABA对α 1β 2γ 2L-GABA AR的激动效应;在膜电位检测研究中,获得GABA激动效应EC 50为(177.72 ± 15.92)nmol/L,Dia变构效应EC 50为(3.63±0.52)μmol/L,拮抗剂Bicuculine拮抗效应IC 50为(538.83±29.55)nmol/L。结论: 通过采用诱导表达策略,成功构建了α 1β 2γ 2L-GABA AR-CHO稳定表达细胞株,该细胞株具有对激动剂、阳性变构剂、拮抗剂特异性检测的药理学功能。 相似文献
6.
In a search for novel analogues of β 3-adrenoceptor (AR) agonists relaxing the bladder for treatment of urinary dysfunction, 2-[4-(2-{[(1 S,2 R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenoxy]-2-methylpropionic acids (1a–e), into which a fibrate-like structure had been incorporated, were synthesised. Compound 1a was found to be a selective β 3-AR agonist in functional assays using the ferret detrusor (β 3-AR), rat uterus (β 2-AR), and rat atrium (β 1-AR); β 3: EC 50=7.8 nM, β 2: IC 50=7,300 nM, β 1: EC 20=23,000 nM. The introduction of a chlorine atom or methyl substituent at the ortho-position on the phenyl ring of 1a further improved β 3-AR selectivity. In an in vivo study, 1a lowered intrabladder pressure (ED 50=31 μg/kg) in rats, without increasing heart rate, in keeping with the in vitro results. Consequently, it is proposed that 1a and its analogues (1b–e), possess β 3-AR agonistic activity in the absence of undesirable β 1- or β 2-AR mediated actions, and may be useful for clinical treatment and pharmacological studies. 相似文献
7.
The γ subunits of voltage-dependent calcium channels influence calcium current properties and may be involved in other physiological functions. Five distinct γ subunits have been described from human and/or mouse. The first identified member of this group of proteins, γ 1, is a component of the L-type calcium channel expressed in skeletal muscle. A second member, γ 2, identified from the stargazer mouse regulates the targeting of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors to the postsynaptic membrane. We report here the identification of three novel γ subunits from rat and mouse as well as the unidentified rat, mouse and human orthologs of the previously described subunits. Phylogenetic analysis of the 24 mammalian γ subunits suggests the following relationship ((((γ 2, γ 3), (γ 4, γ 8)), (γ 5, γ 7)), (γ 1, γ 6)) that indicates that they evolved from a common ancestral γ subunit via gene duplication. Our analysis reveals that the novel γ subunit γ 6 most closely resembles γ 1 and shares with it the lack of a PSD-95/DLG/ZO-1 (PDZ)-binding motif that is characteristic of most other γ subunits. Rat γ subunit mRNAs are expressed in multiple tissues including brain, heart, lung, and testis. The expression of γ 1 mRNA and the long isoform of γ 6 mRNA is most robust in skeletal muscle, while γ 6 is also highly expressed in cardiac muscle. Based on our analysis of the molecular evolution, primary structure, and tissue distribution of the γ subunits, we propose that γ 1 and γ 6 may share common physiological functions distinct from the other homologous γ subunits. 相似文献
8.
β-Arrestins play a role in AT 1 endocytosis by binding the cytoplasmic, C-terminus region T332–S338, the major site of angiotensin II (Ang II)-induced phosphorylation. However, the processes responsible for recruiting β-arrestin to the activated receptor are poorly defined. In this study, we used CHO-K1 and HEK 293 cells expressing wild-type or mutant AT 1 to investigate two possibilities: activated AT 1 induces global relocation of β-arrestins to the plasma membrane or the phosphorylated C-terminus acts as bait to attract β-arrestins. Results obtained using high osmolarity and dominant-negative β-arrestin confirmed that internalization of AT 1 in both CHO-K1 and HEK 293 cells is predominately via clathrin-mediated endocytosis involving β-arrestin, and substitution of T332, S335, T336 and S338 with alanine to preclude phosphorylation markedly attenuated AT 1 internalization. Confocal microscopy revealed that wild-type AT 1 induced a time-dependent translocation of GFP-tagged β-arrestins 1 and 2 to the cell surface. In contrast, the TSTS/A mutant did not traffic β-arrestin 1 at all, and only trafficked β-arrestin 2 weakly. Results of rescue-type experiments were consistent with the idea that both β-arrestins are able to interact with the non-phosphorylated receptor, albeit with much lower affinity and β-arrestin 1 less so than β-arrestin 2. In conclusion, this study shows that the high affinity binding of β-arrestins to the phosphorylated C-terminus is the predominant mechanism of agonist-induced β-arrestin recruitment to the cell surface and AT 1 receptor. 相似文献
9.
The reaction of perrhenate with 2-hydrazinopyrimidine in MeOH–HCl yields [ReCl 3(η 1-NNC 4H 3N 2H)(η 2-HNNC 4H 3N 2)] (1). The analogous reaction with Na 2MoO 4 yields [MoCl 3(η 1-NNC 4H 3N 2H)(η 2-HNNHC 4H 3N 2)] (1a). The reaction of 1 with pyrimidine-2-thiol and triethylamine produces [Re(η 1-C 4H 3N 2S)(η 2-C 4H 3N 2S)(η 1-NNC 4H 3N 2)(η 2-HNNC 4H 3N 2)] (2), while reaction of 1 with the Schiff base HSC 6H 4N=C(H)C 6H 4OH provides [Re(η 3-SC 6H 4N=C(H)C 6H 4O)(η 1-NNC 4H 3N 2)(η 2-HNNC 4H 3N 2)]·0.6CH 2Cl 2 (3·0.6CH 2Cl 2). The analogous hydrazinopyridine complex of the Schiff base, [Re(η 3-SC 6H 4N=C(H)C 6H 4O)(η 1-NNC 5H 4N)(η 2-HNNC 5H 4N)] (4), was also synthesized by reacting [ReCl 3(η 1-NNC 5H 4NH)(η 2-HNNC 5H 4N)] with HSC 6H 4N=C(H)C 6H 4OH. The crystal structures of 1–4 have been determined. 相似文献
10.
Reactions of [(PPh 3) 2Pt(η 3-CH 2CCPh)]OTf with each of PMe 3, CO and Br − result in the addition of these species to the metal and a change in hapticity of the η 3-CH 2CCPh to η 1-CH 2CCPh or η 1-C(Ph)=C=CH 2. Thus, PMe 3 affords [(PMe 3) 3Pt(η 1-C(Ph)=C=CH 2)] +, CO gives both [ trans-(PPh 3) 2Pt(CO)(η 1-CH 2CCPh)] + and [ trans-(PPh 3) 2Pt(CO)(η 1-C(Ph)=C=CH 2)] +, and LiBr yields cis-(PPh 3) 2PtBr(η 1-CH 2CCPh), which undergoes isomerization to trans-(PPh 3) 2PtBr(η 1-CH 2CCPh). Substitution reactions of cis- and trans-(PPh 3) 2PtBr(η 1-CH 2CCPh) each lead to tautomerization of η 1-CH 2CCPh to η 1-C(Ph)=C=CH 2, with trans-(PPh 3) 2PtBr(η 1-CH 2CCPh) affording [(PMe 3) 3Pt(η 1-C(Ph)=C=CH 2)] + at ambient temperature and the slower reacting cis isomer giving [ trans-(PPh 3)(PMe 3) 2Pt(η 1-C(Ph)=C=CH 2)] + at 54 °C . All new complexes were characterized by a combination of elemental analysis, FAB mas spectrometry and IR and NMR ( 1H, 13C{ 1H} and 31P{ 1H}) spectroscopy. The structure of [(PMe 3) 3Pt(η 1-C(Ph)=C=CH 2)]BPh 4·0.5MeOH was determined by single-crystal X-ray diffraction analysis. 相似文献
11.
Reaction of RuCl(η 5-C 5H 5( pTol-DAB) with AgOTf (OTf = CF 3SO 3) in CH 2Cl 2 or THF and subsequent addition of L′ (L′ = ethene (a), dimethyl fumarate (b), fumaronitrile (c) or CO (d) led to the ionic complexes [Ru(η 5-C 5H 5)( pTol-DAB)(L′)][OTf] 2a, 2b and 2d and [Ru(η 5-C 5H 5)( pTol-DAB)(fumarontrile- N)][OTf] 5c. With the use of resonance Raman spectroscopy, the intense absorption bands of the complexes have been assigned to MLCT transitions to the iPr-DAB ligand. The X-ray structure determination of [Ru(η 5-C 5H 5)( pTol-DAB)(η 2-ethene)][CF 3SO 3] (2a) has been carried out. Crystal data for 2a: monoclinic, space group P2 1/ n with A = 10.840(1), b = 16.639(1), C = 14.463(2) Å, β = 109.6(1)°, V = 2465.6(5) Å 3, Z = 4. Complex 2a has a piano stool structure, with the Cp ring η 5-bonded, the pTol-DAB ligand σN, σN′ bonded (Ru-N distances 2.052(4) and 2.055(4) Å), and the ethene η 2-bonded to the ruthenium center (Ru-C distances 2.217(9) and 2.206(8) Å). The C = C bond of the ethene is almost coplanar with the plane of the Cp ring, and the angle between the plane of the Cp ring and the double of the ethene is 1.8(0.2)°. The reaction of [RuCl(η 5-C 5H 5)(PPh) 3 with AgOTf and ligands L′ = a and d led to [Ru(η 5-C 5H 5)(PPh 3) 2(L′)]OTf] (3a) and (3d), respectively. By variable temperature NMR spectroscopy the rottional barrier of ethene (a), dimethyl fumarate (b and fumaronitrile (c) in complexes [Ru(η 5-C 5H 5)(L 2)(η 2-alkene][OTf] with L 2 = iPr-DAB (a, 1b, 1c), pTol-DAB (2a, 2b) and L = PPh 3 (3a) was determined. For 1a, 1b and 2b the barrier is 41.5±0.5, 62±1 and 59±1 kJ mol −1, respectively. The intermediate exchange could not be reached for 1c, and the Δ G# was estimated to be at least 61 kJ mol −. For 2a and 3a the slow exchange could not be reached. The rotational barrier for 2a was estimated to be 40 kJ mol −. The rotational barier for methyl propiolate (HC≡CC(O)OCH 3) (k) in complex [Ru(η 5-C 5H 5)(iPr-DAB) η 2-HC≡CC(O)OCH 3)][OTf] (1 k) is 45.3±0.2 kJ mol −1. The collected data show that the barrier of rotational of the alkene in complexes 1a, 2a, 1b, 2b and 1c does not correlate with the strength of the metal-alkene interaction in the ground state. 相似文献
12.
The use of specific and non-specific antisera for estradiol-17β (E 217β) were compared in the radioimmunoassay of the steroid. The effects of various “blank” mateirials on the standard curve and on the accuracy of recovery of E 217β added to plasma before and after chromatography on LH-20 Sephadex were examined. It was concluded that the use of the specific antiserum (anti-6-oxoE 217β -6-(O-carboxymethyl)oxime-bovine serum albumin(antiE 217β-6-BSA) was an improvement on the non-specific serum anti-E 217β-17-hemisuccinyl-bovine serum albumin (antiE 2 17β-17-BSA) following chromatography of extracts. However, although a precise result could be obtained with the anti-E 217β-6-BSA without the Chromatographic step,
recovery of E 217β added to plasma was only possible if the step was included. The cross-reactivity of estrone (E1)with E217β using anti-E217β-17-BSA as defined by Abraham (J. Clin. Endocr.
, 866 (1969) was examined under conditions of constant and of changing E1:E217β ratio. 相似文献
13.
The polysaccharide chains and the crystallinity of β-glucan in a white sorghum variety, SK 5912 were investigated using chemical and enzymic studies. Mild periodate oxidation and methylation, coupled to descending paper chromatography of products revealed the presence of unresolved non-carbohydrate moiety, 2, 4-and 2, 3-di- O-methyl
-glucose residues (molar ratio; 18:3) and 2, 4, 6-and 2, 3, 6-tri- O-methyl
-glucose residues (molar ratio; 1:14). Paper chromatography of the total acid hydrolysate also revealed a non-carbohydrate spot, identified as protein on the basis of positive Biuret and ninhydrin tests. The O-methyl
-glucose residues suggest two polysaccharide chains designated X and Y. Chain X is formed through linking of β-
-glucopyranosyl residues by (1→3) linkages with 85–86% (1→6) bonds at branch points and constitute about 6–7% of the β-glucan sample. Chain Y, which is 93–94% of the β-glucan polysaccharide chains, constitutes β-
-glucopyranosyl residues in (1→4) linkages and 4–5% (1→6) bonds at branch points. Of the 18 branch points on the X-chains in a given β-glucan sample, about 15 are the Y chains interlinked to the X-chains through their (Y-chains) reducing ends. Both acid and enzyme hydrolyses of the β-glucan suggest two structural organizations, a crystalline and less crystalline granules, based on two first order kinetics. This was correlated by the progress curves obtained during hydrolysis with two purified isoforms of β-glucanases from the sorghum malt. The short and highly branched polysaccharide chains, and longer but less branched polysaccharide chains found in this β-glucan are reminiscent of the structures of amylopectin and amylose, respectively. The Kms of 0.30–0.32 and 0.42–0.50 mg β-glucan/ml for the β-glucanase isoforms also lay credence to both the crystalline forms and the highly polymerised nature of the β-glucan in white sorghum. 相似文献
14.
The aim of the current study was to characterize the effects of chemical ischemia and reperfusion at the transductional level in the brain. Protein kinase C isoforms (, β 1, β 2, γ, δ and ) total levels and their distribution in the particulate and cytosolic compartments were investigated in superfused rat cerebral cortex slices: (i) under control conditions; (ii) immediately after a 5-min treatment with 10 mM NaN 3, combined with 2 mM 2-deoxyglucose (chemical ischemia); (iii) 1 h after chemical ischemia (reperfusion). In control samples, all the PKC isoforms were detected; immediately after chemical ischemia, PKC β 1, δ and isoforms total levels (cytosol + particulate) were increased by 2.9, 2.7 and 9.9 times, respectively, while isoform was slightly reduced and γ isoform was no longer detectable. After reperfusion, the changes displayed by , β 1, γ, δ and were maintained and even potentiated, moreover, an increase in β 2 (by 41 ± 12%) total levels became significant. Chemical ischemia-induced a significant translocation to the particulate compartment of PKC isoform, which following reperfusion was found only in the cytosol. PKC β 1 and δ isoforms particulate levels were significantly higher both in ischemic and in reperfused samples than in the controls. Conversely, following reperfusion, PKC β 2 and isoforms displayed a reduction in their particulate to total level ratios. The intracellular calcium chelator, 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid, 1 mM, but not the N-methyl-d-asparate receptor antagonist, MK-801, 1 μM, prevented the translocation of β 1 isoform observed during ischemia. Both drugs were effective in counteracting reperfusion-induced changes in β 2 and isoforms, suggesting the involvement of glutamate-induced calcium overload. These findings demonstrate that: (i) PKC isoforms participate differently in neurotoxicity/neuroprotection events; (ii) the changes observed following chemical ischemia are pharmacologically modulable; (iii) the protocol of in vitro chemical ischemia is suitable for drug screening. 相似文献
15.
The preparation and structure–activity relationships (SARs) of potent agonists of the human β 3-adrenergic receptor (AR) derived from a 4-aminopiperidine scaffold are described. Examples combine human β 3-AR potency with selectivity over human β 1-AR and/or human β 2-AR agonism. Compound 29s was identified as a potent (EC 50=1 nM) and selective (greater than 400-fold over β 1- with no β 2-AR agonism) full β 3-AR agonist with in vivo activity in a transgenic mouse model of thermogenesis. 相似文献
16.
Two isoforms of 11β-HSD exist; 11β-HSD1 is bi-directional (the reductase usually being predominant) and 11β-HSD2 functions as a dehydrogenase, conferring kidney mineralocorticoid specificity. We have previously described endogenous substances in human urine, “glycyrrhetinic acid-like factors (GALFs)”, which like licorice, inhibit the bi-directional 11β-HSD1 enzyme as well as the dehydrogenase reaction of 11β-HSD2. Many of the more potent GALFs are derived from two major families of adrenal steroids, corticosterone and cortisol. For example, 35-tetrahydro-corticosterone, its derivative, 35-tetrahydro-11β-hydroxy-progesterone (produced by 21-deoxygenation of corticosterone in intestinal flora); 35-tetrahydro-11β-hydroxy-testosterone (produced by side chain cleavage of cortisol); are potent inhibitors of 11β-HSD1 and 11β-HSD2-dehydrogenase, with IC50's in range 0.26–3.0 μM, whereas their 11-keto-35-tetrahydro-derivatives inhibit 11β-HSD1 reductase, with IC50's in range 0.7–0.8 μM (their 35β-derivatives being completely inactive). Inhibitors of 11β-HSD2 increase local cortisol levels, permitting it to act as a mineralocorticoid in kidney. Inhibitors of 11β-HSD1 dehydrogenase/11β-HSD1 reductase serve to adjust the set point of local deactivation/reactivation of cortisol in vascular and other glucocorticoid target tissues, including adipose, vascular, adrenal tissue, and the eye. These adrenally derived 11-oxygenated C21- and C19-steroidal substances may serve as 11β-HSD1- or 11β-HSD2-GALFs. We conclude that adrenally derived products are likely regulators of local cortisol bioactivity in humans. 相似文献
17.
Catecholamines are viewed as major stimulants of diet- and cold-induced thermogenesis and of fasting-induced lipolysis, through the β-adrenoceptors (β 1/β 2/β 3). To test this hypothesis, we generated β 1/β 2/β 3-adrenoceptor triple knockout (TKO) mice and compared them to wild type animals. TKO mice exhibited normophagic obesity and cold-intolerance. Their brown fat had impaired morphology and lacked responses to cold of uncoupling protein-1 expression. In contrast, TKO mice had higher circulating levels of free fatty acids and glycerol at basal and fasted states, suggesting enhanced lipolysis. Hence, β-adrenergic signalling is essential for the resistance to obesity and cold, but not for the lipolytic response to fasting. 相似文献
18.
目的: 建立动脉逐搏取血血气分析法,在人体实验中验证呼吸调控核心信号——PaO 2,PaCO 2和[H +]a是受呼吸影响的周期性、波浪式变化信号,而不是传统理念上误认的稳定水平信号。 方法: 选择心功能正常、Allen试验阴性需要监测动脉血流动力学变化的患者6例。在左侧桡动脉穿刺,连接肝素化塑化管(3 mm×1 000 mm),注满血液并计数血液注满所需心跳次数。用止血钳将塑化管钳闭成与心跳次数相对应的分段后,迅速置于冰水中,立即进行血气分析。选取每位患者的2个典型波浪式周期,用于分析2对最高-最低和最低-最高共4个测定值,取平均值。对相邻最高和最低值作统计学配对 t检验。 结果: 血液注满塑化管需要16±2次心跳,均覆盖超过2个呼吸周期。每个呼吸周期是5±0.6次心跳。PaO 2、PaCO 2、[H +]a和SaO 2都呈现出明显的波浪式变化(相邻高点与低点比较, P<0.05),PaO 2、PaCO 2、[H +]a和SaO 2的波浪幅度分别是(11.28±1.13)mmHg,(1.77±0.89)mmHg,(1.14±0.35)nmol/L和(0.52±0.44)%;波浪幅度分别是其平均值的(7.7±1.1)%,(5.1±2.5)%,(3.1±1.0)%和(0.5±0.4)%。 结论: 动脉延长管连续取血,按心跳次数分隔血样,血气分析法简单易行,为验证动脉血气受呼吸影响的周期性波浪式信号提供了可靠证据。本方法为原创,技术操作层面仍需提高熟练程度,增加志愿者和试验样本的数量进一步探索此类信号的临床检测可靠性及其与临床疾病的关系。 相似文献
19.
The Pt 2 (II) isomeric terminal hydrides [(CO)(H)Pt(μ-PBu t 2) 2Pt(PBu t 2H)]CF 3SO 3 (1a), and [(CO)Pt(μ-PBu t 2) 2Pt(PBu t 2H)(H)]CF 3SO 3 (1b), react rapidly with 1 atm of carbon monoxide to give the same mixture of two isomers of the Pt 2 (I) dicarbonyl [Pt 2(μ-PBu t 2)(CO) 2(PBu t 2H) 2]CF 3SO 3 (3-Pt); the solid state structure of the isomer bearing the carbonyl ligands pseudo- trans to the bridging phosphide was solved by X-ray diffraction. A remarkable difference was instead found between the reactivity of 1a and 1b towards carbon disulfide or isoprene. In both cases 1b reacts slowly to afford [Pt 2(μ-PBu t 2)(μ,η 2,η 2-CS 2)(PBu t 2H) 2]CF 3SO 3 (4-Pt), and [Pt 2(μ-PBu t 2)(μ,η 2,η 2-isoprene) (PBu t 2H) 2]CF 3SO 3 (6-Pt), respectively. In the same experimental conditions, 1a is totally inert. A common mechanism, proceeding through the preassociation of the incoming ligand followed by the P---H bond formation between one of the bridging P atoms and the hydride ligand, has been suggested for these reactions. 相似文献
20.
An overview of the application of kinetic methods to the delineation of 17β-hydroxysteroid dehydrogenase (17β-HSD) heterogeneity in mammalian tissues is presented. Early studies of 17β-HSD activity in animal liver and kidney subcellular fractions were suggestive of multiple forms of the enzyme. Subsequently, detailed characterization of activity in cytosol and subcellular membrane fractions of human placenta, with particular emphasis on inhibition kinetics, yielded evidence of two kinetically-differing forms of 17β-HSD in that organ. Gene cloning and transfection experiments have confirmed the identity of these two proteins as products of separate genes. 17β-HSD type 1 is a cytosolic enzyme highly specific for C 18 steroids such as 17β-estradiol (E 2) and estrone (E 1). 17β-HSD type 2 is a membrane bound enzyme reactive with testosterone (T) and androstenedione (A), as well as E 2 and E 1. Useful parameters for the detection of multiple forms of 17β-HSD appear to be the E 2/T activity ratio, NAD/NADP activity ratios, steroid inhibitor specificity and inhibition patterns over a wide range of putative inhibitor concentrations. Evaluation of these parameters for microsomes from samples of human breast tissue suggests the presence of 17β-HSD type 2. The 17β-HSD enzymology of human testis microsomes appears to differ from placenta. Analysis of human ovary indicates granulosa cells are particularly enriched in the type 1 enzyme with type 2-like activity in stroma/theca. Mouse ovary appears to contain forms of 17β-HSD which differ from 17β-HSD type 1 and type 2 in their kinetic properties. 相似文献
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