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1.
In the 12-day-old rat cochlea, the synthesis of inositol phosphates (IPs) can be activated via M3 cholinoceptors. This stimulation is blocked by ototoxins (mercury, ethacrynate, cisplatin, neomycin), drugs with side effects that lead to damage of hair cells and strial cells. As these toxic effects can be reversed in vivo by thiol molecules, we investigated whether modifications of thiol compounds could be involved in ototoxin-induced inhibition of the IP turnover in the cochlea. For this purpose, we assessed whether the sulphhydryl-modifying reagents N -ethylmaleimide and cadmium modify the carbachol-stimulated formation of IPs in the 12-day-old rat cochlea. Both molecules inhibit the carbachol effect on a dose-dependent way without altering the basal metabolism of IPs. As cadmium may block some calcium channels, the effect of verapamil, another calcium channel antagonist, was tested. Verapamil (1 –50 μM) does not alter carbachol-evoked IP formation, suggesting that the inhibitory effect of cadmium is not due to a calcium influx block. Binding experiments with the muscarinic ligand quinuclidinyl benzylate (QNB) showed that the sulphhydryl-modifying reagents do not displace QNB from binding sites. Combining ototoxins and reagents shows that N -ethylmaleimide acts synergistically with all ototoxins but ethacrynate while cadmium does so only with mercury. Both N -ethylmaleimide and cadmium have additive effects with ethacrynate. As a supplement, disulphide bond-modifying agents do not alter the carbachol-enhanced metabolism of IPs. These results suggest that molecules having thiol-modifying properties inhibit the carbachol-induced turnover of IPs without acting at the muscarinic sites. Since thiol modifiers and ethacrynate share similar features in both QNB binding and IP response it is hypothesized that they strike common targets, possibly G proteins. 相似文献
2.
This study sought to pharmacologically characterize bradykinin receptors on SV40-immortalized human trabecular meshwork (HTM3) cells. Phosphoinositide (PI) turnover studies were conducted using [3H]myo-inositol-labeled HTM3 cells and anion exchange chromatography to quantify [3H]inositol phosphates generated in response to bradykinin (BK) and various BK analogs. The blockade of these responses was studied using two potent and receptor-subtype selective antagonists. BK and T-kinin (Ile-Ser-BK; TK) induced a 4.2–4.4 fold stimulation of PI turnover above base levels at 1–10 μM. Several other peptides unrelated to BK, including angiotensin II, endothelin, cholecystokinin, bombesin and peptide YY tested at 1–10 μMwere essentially inactive. The molar potencies (EC50) of BK, TK and close analogs were: BK=4.5±0.5 nM(n=6), Lys-BK=6.5±0.7 nM(n=3), TK=38.8±6.6 nM(n=8), Met-Lys-BK=41.5±13.4 nM(n=4), Des-Arg9-BK=2093±626 nM(n=4). All the latter BK-related peptides>were full agonists. The actions of BK and TK were potently and competitively antagonized by Hoe-140 (molar potency=0.6–1 nM;pA2n=8.97–9.21,n=3–4) and byD-Arg0[Hyp3,-Thi5,8,-DPhe7]-BK (molar potency=251 nM;-log potency, pKb=6.6), two selective B2-type BK antagonists. In conclusion, rank order of potency of BK agonists and the blockade of BK- and TK-induced PI turnover by the selective antagonists are consistent with the classification of the BK receptors on HTM3 cells as the B2-receptor subtype. 相似文献
3.
Summary The present report compares the effects of different membrane phospholipid (PL)-cholesterol compositions on the kinetics of liposome-mediated formation of calcium phosphates from metastable solutions (2.25 mM CaCl2; 1.5 mM KH2PO4) at 22°C, pH 7.4 and 240 mOsm. In most experiments, the liposomes were composed of 7:2:X mixtures of phosphatidylcholine (PC), neutral or acidic phospholipids, and cholesterol (Chol, X=0, 10, 35, or 50 mol%). The neutral phospholipids (NPL) examined, in addition to PC, were phosphatidylethanolamine (PE) and sphingomyelin (Sph), and the acidic phospholipids (APL) examined were dicetylphosphate (DCP), dioleolylphosphatidylglycerol (DOPG), dioleolylphosphatidic acid (DOPA), phosphatidylserine (PS) and phosphatidylinositol (PI). The 7:2:X liposomes did not initiate mineralization in metastable external solutions per se or, with the exception of DOPA, show extensive Ca-PL binding. However, solution Ca2+ losses due to precipitation occurred when the liposomes were encapsulated with 50 mM KH2PO4 and made permeable to external Ca2+ with X-537A. The extent of these Ca2+ losses was sensitive to both the phospholipid and Chol makeup of the membrane. Moderate-to-extensive intraliposomal precipitation occurred in all 7PC:2APL and 7PC:2NPL liposomes containing 0 or 10 mol% Chol. In contrast, at 50 mol% Chol, mineralization inside all liposomes was negligible. The only significant discriminating effect on internal mineralization among the different phospholipids was observed at 35 mol% Chol, where mineral accumulations ranged from negligible to moderate. At 0 or 10 mol% Chol, extraliposomal precipitation was extensive in all but DOPA- and PS-containing liposomes. However, onece intraliposomal yields declined at the higher Chol levels, external mineralization was either delayed or totally blocked in all liposome preparations. Other experiments showed that Sph substituted for PC in 7NPL:2DCP:1Chol liposomes totally blocked both intra- and extraliposomal precipitaiton. PE substituted in this manner, however, blocked only extraliposomal precipitation. The results of this study suggest that interference of the membrane transport processes controlling intraliposomal precipitation [15] by high (50 mol%) Chol levels is not significantly compromised by the specific APL or NPL incorporated in the membrane. Similarly, the data suggest that Chol does not directly affect the specfic interactions of the different membrane APLs with the mineral phase. On the other hand, the substitution of other NPLs for PC can affect the role of APLs such as DCP in liposome-mediated mineralization. 相似文献
4.
磷酸钙骨水泥修复良性骨肿瘤骨缺损 总被引:1,自引:0,他引:1
目的:研究磷酸钙骨水泥(CPC)修复良性骨肿瘤刮除术后遗留的骨缺损的临床应用。方法:应用CPC修复33例患者良性骨肿瘤刮除术后遗留的骨缺损。患者平均年龄38岁,肿瘤类型依次为骨纤维结构不良、骨巨细胞瘤、骨囊肿、动脉瘤样骨囊肿、软骨粘液样纤维瘤、非骨化性纤维瘤、骨母细胞瘤,观察患者术中CPC固化时间,术后全身及切口局部反应,血钙、磷值变化,X线片和CT扫描,平均随访时间19个月。结果:全部患者未见明显不良反应,血钙、磷值未见升高,X线片显示骨缺损处均填充良好,随访见所有患者均有CPC降解和骨替代现象发生。结论:良性骨肿瘤刮除后利用CPC填充修复骨缺损,可充分填充骨肿瘤刮除后不规则瘤腔,即刻恢复骨的强度.经骨替代后可真正完成骨修复。术式简单.并发症少。 相似文献
5.
6.
A liposome-centered endogenous precipitation method was used to investigate the effect of ultrafilterable fragments from the enzymatic digestion of rat chondrosarcoma aggrecan on the formation of insoluble calcium phosphate salts in buffered solutions at pH 7.4 and 22°C. Unlike the intact aggrecan and its major chondroitin sulfate and core protein components, disaccharide units from chondroitinase degradation of the aggrecan and small (<3kg/mol molecular weight) fragments from protease digestion of the core structure were found to be only weakly inhibitory toward mineral formation. Corresponding reductions in Ca2+-binding indicate that these fragments were unable to adsorb to active sites on the apatite surface for long enough periods to significantly hinder crystal growth. The data suggest that controlled enzymatic breakdown of aggrecan may be one possible mechanism by which the calcification of growth plate cartilage is allowed to advance in vivo.The commercial materials and equipment identified in this paper do not imply recommendation or endorsement by the National Institute of Standards and Technology nor is the material and equipment necessarily the best available for the purpose. 相似文献
7.
8.
Chuen -Mao Yang Hui -Liang Tsao Chi -Tso Chiu Lir -Wan Fan Sheu -Meei Yu 《Pflügers Archiv : European journal of physiology》1996,432(4):708-716
The effects of increases in cellular adenosine 3′5′-cyclic monophosphate (cAMP) on 5-hydroxytryptamine-(5-HT-) induced generation
of inositol phosphates (IPs) and increases in intracellular Ca2+ ([Ca2+]i) were investigated using canine cultured tracheal smooth muscle cells (TSMCs). Cholera toxin and forskolin induced concentration-
and time-dependent cAMP formation with half-maximal effects (−logEC50) produced at concentrations of 7.0 ± 0.5 and 4.9 ± 0.4 respectively. Pretreatment of TSMCs with either forskolin or dibutyryl
cAMP inhibited 5-HT-stimulated responses. Even after treatment for 24h, these agents still inhibited the 5-HT-induced Ca2+ mobilization. The inhibitory effects of these agents produced both depression of the maximal response and a shift to the
right of the concentration response curves of 5-HT. The water-soluble forskolin analogue L-858051 [7-deacetyl-7β-(γ-N-methylpiperazino)-butyryl forskolin] significantly inhibited the 5-HT-stimulated accumulation of IPs. In contrast, the addition
of 1,9-dideoxy forskolin, an inactive forskolin analogue, had little effect on this response. Moreover, SQ-22536 [9-(tetrahydro-2-furanyl)-9-H-purin-6-amine], an inhibitor of adenylate cyclase, and both H-89 [N-(2-aminoethyl)-5-isoquinolinesulphonamide] and HA-1004[N-(2-guanidinoethyl)-5-isoquinolinesulphonamide], inhibitors of cAMP-dependent protein kinase (PKA), attenuated the ability
of forskolin to inhibit the 5-HT-stimulated accumulation of IPs. These results suggest that activation of cAMP/PKA was involved
in these inhibitory effects of forskolin. The AlF4
−-induced accumulation of IPs was inhibited by forskolin, suggesting that G protein(s) are directly activated by AlF4
−- and uncoupled from phospholipase C by forskolin treatment. These results suggest that activation of cAMP/PKA might inhibit
the 5-HT-stimulated phosphoinositide breakdown and consequently reduce the [Ca2+]i increase or inhibit both responses independently.
Received: 14 March 1996/Accepted: 10 April 1996 相似文献
9.
Beneke R Beyer T Jachner C Erasmus J Hütler M 《European journal of applied physiology》2004,92(4-5):518-523
It is speculated that anaerobic metabolism is the predominant source of energy in karate kumite. However, no experimental proof is currently available. The metabolic cost and fractions of aerobic and anaerobic energy of karate kumite fighting were investigated. Ten male nationally or internationally ranked karateka [means (SD) age 26.9 (3.8) years, height 1.80 (0.08) m, mass 77.2 (12.8) kg] performed two to four fights scheduled and judged like a championship. Oxygen uptake was measured continuously with a portable spirometric device. Blood lactate was determined immediately before, and minute by minute after, each fight. Aerobic, anaerobic alactic and anaerobic lactic energy were calculated from oxygen uptake during the fight (VO2), the fast component of the post-fight oxygen uptake (VO2PCr) above resting values and changes in blood lactate concentration (Net-BLC), respectively. Altogether, 36 fights lasting 267 (61) s were analysed. The referees decisions caused an activity-to-break ratio of approximately 2:1. VO2, VO2PCr, and Net-BLC per fight were 165.3 (52.4) ml.kg–1, 32.2 (7.2) ml.kg–1and 4.2 (1.9) mmol.l–1; the overall energy cost above rest was 334.3 (86.3) kJ per fight. Fractions of aerobic, anaerobic alactic, and lactic energy sources were 77.8 (5.8)%, 16.0 (4.6)%, and 6.2 (2.4)%, respectively. The results indicate a high metabolic rate in karate kumite. However, the acyclic activity profile implies that aerobic metabolism is the predominant source of energy and there is anaerobic supplementation, mainly by high-energy phosphates. 相似文献
10.
Agnès Conjard Heidemarie Peuker D. Pette 《Pflügers Archiv : European journal of physiology》1998,436(6):962-969
Energy-rich phosphates, [ATP]/[ADPfree] ratios, and the myosin heavy chain (MHC) complement were determined in single fibres from normal rabbit muscles, and in
fibres isolated from tibialis anterior muscle undergoing fast-to-slow conversion by chronic low-frequency stimulation (CLFS).
In normal muscles, energy-rich phosphate contents and [ATP]/[ADPfree] ratios could thus be assigned to different MHC-based fibre types. Phosphocreatine (PCr) contents and [ATP]/[ADPfree] ratios differed markedly between fast- and slow-twitch fibres, as well as within the fast fibre subtypes. Both magnitudes
were approximately twofold higher in the fastest (type IIB) fibres as compared to the slowest (type I) fibres. According to
PCr contents and [ATP]/[ADPfree] ratios pure and hybrid fibres were aligned in an order similar to that determined by their contractile properties and myofibrillar
ATPase activities. CLFS for up to 30 days induced pronounced decreases in PCr and [ATP]/[ADPfree] which attained levels twofold lower than in normal slow-twitch fibres. In both normal and stimulated muscles, PCr and [ATP]/[ADPfree] ratios were correlated, indicating their equilibrium in the different fibre types. The relationship detected between MHC
isoform expression and the [ATP]/[ADPfree] ratio suggests that the drastic and persistent depression of the cellular energy state may act as an important signal initiating
fast-to-slow transformation processes in muscle fibres.
Received: 26 June 1998 / Accepted: 31 July 1998 相似文献