共查询到20条相似文献,搜索用时 15 毫秒
1.
Abstract: The influence of putrescine, spermidine, spermine, and some aliphatic α,ω-diamines on the uptake of neurotransmitters by rat forebrain synaptosomes was investigated. Choline uptake was most effectively inhibited by spermine (IC50 = 0.22 m M ), less so by spermidine (IC50 = 4.0 m M ), but not by putrescine (IC50 > 100 m M ). At 10 m M, 1,3-diaminopropane, cadaverine, and 1,8-diaminooctane all inhibited choline uptake by 50% or more. Spermine and spermidine inhibited the uptake of dopamine with IC50 values of 2.7 and 2.2 m M , respectively. Putrescine was only slightly inhibitory (IC50 = 17.3 m M ) and the other diamines were inactive. The uptake of γ-aminobutyrate (GABA) was only slightly inhibited (15–40%) by the polyamines at 10 m M . With the exception of inhibition of glycine uptake by 1,8-diaminooctane (60%) and of glutamate uptake by cadaverine (35%) none of the polyamines, tested at 10 m M , affected the uptake of adenosine, glutamate, and glycine significantly. A possible modulatory role for polyamines in synaptic transmission through interaction by negatively charged groups of the synaptic membrane with the polycationic compounds is discussed. 相似文献
2.
Fumi Katoh Kazuo Kitamura Hiromi Niina Ryuichi Yamamoto Hisanori Washimine †Kenji Kangawa Yoshitaka Yamamoto Hideyuki Kobayashi Tanenao Eto Akihiko Wada 《Journal of neurochemistry》1995,64(1):459-461
Abstract: In cultured bovine adrenal medullary cells, stimulation of nicotinic receptors by carbachol evoked the Ca2+ -dependent exocytotic cosecretion of proadrenomedullin N-terminal 20 peptide (PAMP) (EC50 = 50.1 µ M ) and catecholamines (EC50 = 63.0 µ M ), with the molar ratio of PAMP/catecholamines secreted being equal to the ratio in the cells. Addition of PAMP[1–20]NH2 inhibited carbachol-induced 22 Na+ influx via nicotinic receptors (IC50 = 2.5 µ M ) in a noncompetitive manner and thereby reduced carbachol-induced 45 Ca2+ influx via voltage-dependent Ca2+ channels (IC50 = 1.0 µ M ) and catecholamine secretion (IC50 = 1.6 µ M ). It did not alter high K+ -induced 45 Ca2+ influx via voltage-dependent Ca2+ channels or veratridine-induced 22 Na+ influx via voltage-dependent Na+ channels. PAMP seems to be a novel antinicotinic peptide cosecreted with catecholamines by a Ca2+ -dependent exocytosis in response to nicotinic receptor stimulation. 相似文献
3.
Abstract: The effect of phloretin on prostaglandin (PG) F2α -induced phosphoinositide hydrolysis and elevation of intracellular Ca2+ concentration was examined in cultured rat astrocytes. Phloretin inhibited PGF2α (1 μ M )-induced phosphoinositide hydrolysis in a concentration-dependent manner with an IC50 value of 16 μ M . The inhibitory action of phloretin was specific for PGs. The addition of increasing concentrations of phloretin caused progressive shifts of the dose-response curves of PGF2α to the right. In digitoninpermeabilized astrocytes, phloretin (100 μ M ) inhibited the stimulation induced by PGF2α (1 μ M ) plus GTPγS (50 μ M ) without affecting that induced by GTPγS alone. PGF2α at 1 μ M transiently increased astrocytic intracellular Ca2+ concentration in 39% of the cells tested. The response was completely blocked by 100 μ M phloretin and the calcium response recovered again after washing out phloretin. These results suggest that phloretin is an antagonist of PGF2α receptor linked to phospholipase C in astrocytes. 相似文献
4.
Ethanol in the stems of trees 总被引:3,自引:0,他引:3
Acetaldehyde and ethanol are usually thought to be produced in plant tissues as a mechanism to tolerate hypoxic conditions. We have found acetaldehyde and ethanol to be common in the vascular cambium and in the transpiration stream of trees. In nonflooded trees, acetaldehyde and ethanol concentrations averaged 130 and 40 μ M in the cambium and 130 and 50 μ M in the xylem sap, respectively. Ethanol concentrations in the transpiration stream and the cambium increased to as much as 5 m M upon flooding. Ethanol concentrations in the vascular cambium of Populus deltoides could not be eliminated by placing logs from nonflooded trees in a pure oxygen environment for as long as 96 h, but increased by almost 3 orders of magnitude when logs were exposed to low external partial pressures of O2 . These results suggest that the vascular cambium was not hypoxic, despite the presence of acetaldehyde, ethanol and the enzymes for their synthesis. 相似文献
5.
John J. Woodward 《Journal of neurochemistry》1994,62(3):987-991
Abstract: N -Methyl- d -aspartate (NMDA; 500 μ M ) stimulated the net release of preloaded tritiated norepinephrine from rat hippocampal slices. Both ethanol and the competitive glycine antagonist 7-chlorokynurenic acid (7-CK) dose-dependently inhibited NMDA-stimulated release without affecting basal, nonstimulated efflux. These inhibitory effects were readily reversed upon washout of the drugs. Over the concentration range tested (25–200 m M ), ethanol inhibited ∼65% of NMDA-stimulated release with an estimated IC50 of ∼70 m M . In contrast, 7-CK fully inhibited release (>95%) at a concentration of 30 μ M with half-maximal inhibition occurring at ∼2 μ M . The combination of 7-CK (1–30 μ M ) and ethanol (25–100 m M ) had an additive inhibitory effect on NMDA-stimulated release but did not alter the inhibitory potency of 7-CK. Calculated IC50 values for 7-CK in the presence of 25, 50, or 100 m M ethanol were (mean × SEM; μ M ) 2.33 (0.11), 2.38 (0.23), and 1.99 (0.30), respectively. 7-CK (3 μ M ) inhibited NMDA-stimulated [3 H]norepinephrine release by ∼50%. This inhibition was fully attenuated by the addition of the glycine agonistserine with complete reversal occurring at 30 μ M d -serine. Increasing the 7-CK concentration to 10 μ M shifted the d -serine dose-effect curve to the right in a parallel fashion as expected for a competitive antagonist. In contrast, the inhibitory effects of ethanol or the combination of 7-CK (3 μ M ) and ethanol (25 or 50 m M ) were not reversed by the addition of d -serine (0.1–1,000 μ M ). Together, these results suggest that ethanol's inhibition of NMDA-stimulated [3 H]norepinephrine release from hippocampal slices is not due to a simple competitive interaction with the glycine site on the NMDA receptor. 相似文献
6.
Abstract: Phosphatidylinositol (PI) 3-kinase is activated by a variety of agents, including various growth factors, and has been proposed to play a role in initiation of cell growth, proliferation, and differentiation. We here investigate the effect of various membrane lipids on PI 3-kinase immunopurified from human SH-SY5Y neuroblastoma cells. CDP-diacylglycerol (CDP-DAG) inhibited PI 3-kinase activity with an IC50 of 6 µ M . Phosphatidate (PA) was also inhibitory (IC50 = 38 µ M ) as was lysophosphatidate. Neither DAG nor any of the other phospholipids examined affected PI 3-kinase activity. The results offer the possibility that CDP-DAG or PA at critical membrane sites may exert functionally significant metabolic regulation at the point of convergence of the PI 3-kinase-directed and the PI 4-kinase-directed phosphoinositide signal transduction pathways. 相似文献
7.
O. M. Larsson P. Thorbek P. Krogsgaard-Larsen A. Schousboe 《Journal of neurochemistry》1981,37(6):1509-1516
Abstract: Two groups of GABA (γ-aminobutyric acid) analogues, one comprising derivatives of β-proline and the other compounds structurally related to nipecotic acid, were investigated as potential inhibitors of high-affinity GABA transport in neurons and glial cells, as well as displacers of GABA receptor binding. In addition to cis -4-hydroxynipecotic acid, which is known as a potent inhibitor of GABA uptake, homo-β-proline was the only compound which proved to be a potent inhibitor of glial as well as neuronal GABA uptake. IC50 values for GABA uptake into glial cells and brain cortex "prisms" were 20 and 75 μM, respectively, and the IC50 value obtained for GABA uptake into cultured neurons was 10 μM. A kinetic analysis of the action of homo-β-proline on GABA uptake into cultured astrocytes and neurons showed that this compound acts as a competitive inhibitor of GABA uptake in both cell types. From the apparent K m values, K i values for homo-β-proline of 16 and 6 μM could be calculated for glial and neuronal uptake, respectively. This mechanism of action strongly suggests that homo-β-proline interacts with the GABA carriers. Furthermore, homo-β-proline also displaced GABA from its receptor with an IC50 value of 0.3 μM. The cis -4-hydroxynipecotic acid analogues, cis- and trans-4-mercaptonipecotic acid, had no inhibitory effect on glial or neuronal GABA uptake. Other SH reagents, PCMB, NEM and DTNB, were shown to be relatively weak inhibitors of GABA uptake into cultured astrocytes, suggesting that SH groups are not directly involved in the interaction between GABA and its transport carrier. 相似文献
8.
Characterization of Ethanol-Sensitive and Insensitive Fibroblast Cell Lines Expressing Human L1 总被引:3,自引:2,他引:1
Abstract: Ethanol inhibits L1-mediated cell-cell adhesion in fibroblast cell lines stably transfected with human L1. Here we show that this action of ethanol is present in only a subset of transfected NIH/3T3 and L cell clonal cell lines. All L1-expressing cell lines had higher levels of cell adhesion than cell lines transfected with empty vector. In all ethanol-sensitive cell lines, L1-mediated adhesion was inhibited by ethanol (IC50 5–10 m M ), 2 m M butanol, but not 5 m M pentanol. In contrast, ethanol-insensitive cell lines were not inhibited by up to 200 m M ethanol, 2 m M butanol, or 5 m M pentanol. Ethanol sensitivity or insensitivity was a stable property of each cell line and was not associated with differences in electrophoretic mobility, abundance, or cell surface localization of L1. Fab fragments prepared from anti-L1 polyclonal antisera inhibited cell adhesion only in the ethanol-sensitive cell lines. These data suggest that L1 may exist in an alcohol-sensitive or an alcohol-insensitive state that may be governed by host cell factors. 相似文献
9.
Ryoichi Ishitani Mitsutoshi Kimura Masami Takeichi De-Maw Chuang 《Journal of neurochemistry》1994,63(6):2080-2085
Abstract: Tryptamine dose-dependently increased phosphoinositide (PI) hydrolysis by approximately fourfold in primary cultures of rat cerebellar granule cells (EC50 = 56 µ M ). The PI response stimulated by tryptamine was dependent on the presence of extracellular Ca2+ and Na+ . Tryptamine-induced PI breakdown could be partially inhibited by pretreatment with 4β-phorbol 12-myristate 13-acetate but not pertussis toxin. The presence of tryptamine markedly attenuated PI responses induced by norepinephrine (NE) and carbachol, with no apparent effect on the responses to 5-hydroxytryptamine and glutamate. The inhibition of NE- and carbachol-induced PI turnover by tryptamine was dose dependent with IC50 values of ∼0.4 and ∼2.5 m M , respectively. Pretreatment of cells with tryptamine (0.5 m M ) also attenuated NE- and carbachol-induced PI turnover, but failed to affect 5-hydroxytryptamine- and glutamate-induced responses. Furthermore, ketanserin, atropine, and prazosin did not have any effect on inositol phosphate formation induced by tryptamine. These observations indicate that tryptamine markedly increased Ca2+ - and Na+ -dependent PI turnover in cerebellar neurons and selectively inhibited NE- and carbachol-induced PI hydrolysis. 相似文献
10.
Richard E. Roberts Charles A. Marsden David A. Kendall 《Journal of neurochemistry》1997,69(3):1291-1299
Abstract: Recent in vivo microdialysis studies have demonstrated the presence of extracellular levels of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3 ] that can be increased in a concentration-dependent manner by muscarinic receptor activation. The aim of the present study was to determine whether extracellular levels of Ins(1,4,5)P3 could be measured in vitro. Despite rapid increases in internal Ins(1,4,5)P3 levels after stimulation with 1 m M carbachol, there was no change in external levels in both rat brain cortical slices and human neuroblastoma SH-SY5Y cells. Suprafusion of myo -[3 H]inositol-prelabelled hippocampal slices with 1 m M carbachol caused an increase in 3 H-inositol phosphates over basal levels in the perfusate after 10 min, reaching a peak (223 ± 56% of basal) 20 min after suprafusion with carbachol was started. This response to carbachol was potentiated in the presence of 30 m M K+ . Analysis of the individual 3 H-inositol phosphates in the perfusate revealed that levels of [3 H]inositol monophosphate, [3 H]inositol bisphosphate, [3 H]inositol trisphosphate, and [3 H]inositol tetrakisphosphate were all significantly increased. A similar increase in extracellular 3 H-inositol phosphates was demonstrated in SH-SY5Y cells incubated with 1 m M carbachol for 30 min. This response was again enhanced by 30 m M K+ , although the intracellular response was not potentiated. Possible roles for extracellular inositol phosphates are discussed. 相似文献
11.
Expression and Regulation of Types I and II Inositol 1,4,5-Trisphosphate Receptors in Rat Cerebellar Granule Cell Preparations 总被引:2,自引:0,他引:2
Jon Oberdorf Mary Lou Vallano Richard J. H. Wojcikiewicz 《Journal of neurochemistry》1997,69(5):1897-1903
Abstract: Previous studies have shown that as rat cerebellar granule cell cultures differentiate in the presence of 25 m M KCl, they "up-regulate" their ability to form inositol phosphates and release Ca2+ from internal stores in response to the activation of phosphoinositidase C-linked muscarinic and metabotropic receptors. Here we show that they simultaneously up-regulate their ability to respond to inositol 1,4,5-trisphosphate (InsP3 ) by increasing InsP3 receptor (InsP3 R) expression. In contrast, if granule cells are maintained at the more physiological KCl concentration of 5 m M , most cells undergo apoptosis, although a significant number survive. The surviving cells, however, express few InsP3 Rs, suggesting that an influx of Ca2+ through voltage-dependent channels is required for InsP3 R up-regulation. In addition, we have determined that these cultures express two genetically distinct InsP3 R types, but that only one, the type I receptor, is expressed in granule cells. Type II receptors are also present but are found exclusively in astrocytes, which are a minor contaminant of granule cell cultures. This segregation of InsP3 R types explains a previous observation, showing that the muscarinic agonist carbachol causes the reduction or "down-regulation" of type I but not type II InsP3 Rs. 相似文献
12.
Sarah Grimwood Elizabeth Gilbert C. Ian Ragan Peter H. Hutson 《Journal of neurochemistry》1996,66(6):2589-2595
Abstract: A 45 Ca2+ influx assay has been used to investigate the pharmacology of stably expressed recombinant human NR1a/NR2A and NR1a/NR2B N -methyl- d -aspartate (NMDA) receptors. Inhibition of glutamate-stimulated 45 Ca2+ influx by six glycine-site antagonists and inhibition of glycine-stimulated 45 Ca2+ influx by five glutamate-site antagonists revealed no significant differences between affinity values obtained for NR1a/NR2A and NR1a/NR2B receptors. The polyamine site agonist spermine showed differential modulation of glutamate- and glycine-stimulated 45 Ca2+ influx for recombinant NMDA receptors, inhibiting and stimulating 45 Ca2+ influx into cells expressing NR1a/NR2A receptors (IC50 = 408 µ M ) and NR1a/NR2B receptors (EC50 = 37.3 µ M ), respectively. The antagonist ifenprodil was selective for NR1a/NR2B receptors (IC50 = 0.099 µ M ) compared with NR1a/NR2A receptors (IC50 = 164 µ M ). The effects of putative polyamine site antagonists, redox agents, ethanol, and Mg2+ and Zn2+ ions were also compared between NR1a/NR2A and NR1a/NR2B receptors. This study demonstrates the use of 45 Ca2+ influx as a method for investigating the pharmacology of the numerous modulatory sites that regulate the function of recombinant human NMDA receptors stably expressed in L(tk-) cells. 相似文献
13.
Catherine Van Renterghem Paul Vigne Christian Frelin 《Journal of neurochemistry》1995,65(3):1274-1281
Abstract: A charybdotoxin-sensitive, Ca2+ -activated K+ channel was identified in cultured rat brain capillary endothelial cells by using conventional single-channel recording techniques and 86 Rb+ -influx and efflux experiments. Channel activity was dependent on the presence of Ca2+ on the cytosolic face of the membrane with a threshold concentration of 100 n M . It was inhibited by charybdotoxin (IC50 30 n M ) and quinine (IC50 0.1 m M ) but not by apamin. K(Ca) channels showed unusual inward rectifying properties under asymmetrical ionic conditions. They were activated by endothelin-1 (EC50 0.7 n M ) and endothelin-3 (EC50 7–10 n M ). The actions of endothelins were prevented by BQ-123 ( K i = 8 n M ) in a competitive fashion, hence suggesting the involvement of an ETA -receptor subtype. The channel activity was unaffected by cyclic AMP- or cyclic GMP-elevating agents. The possible role of the intermediate conductance, Ca2+ -activated K+ channels for mediating K+ movements across the blood-brain barrier is discussed. 相似文献
14.
15.
C. Minisclou L. Rouquier J. Benavides B. Scatton Y. Claustre 《Journal of neurochemistry》1994,62(2):557-562
Abstract: The extracellular concentration of inositol 1,4,5-trisphosphate (IP3 ) has been monitored in the ventral hippocampus of the anesthetized rat by using a microdialysis technique coupled to a radioreceptor assay. Three hours after the implantation of the cannula, basal extracellular concentration of IP3 (corrected for a 9% recovery) was 71 n M (0.39 pmol/60-µl fraction) and remained stable for at least 5 h. Local infusion of carbachol for 60 min caused a significant concentration-related increase in extracellular IP3 levels (0, 24, and 57% at 1, 50, and 100 µ M , respectively). Acetylcholine (100 µ M ) and muscarine (100 µ M ) increased IP3 outflow by 40 and 42%, respectively. The effect of carbachol was fully prevented by coinfusion of 10 µ M pirenzepine and reduced by 1 µ M tetrodotoxin indicating that the carbachol response is mediated by neuronal muscarinic receptors. These data demonstrate the feasibility of using microdialysis and a radioreceptor assay to measure IP3 in the extracellular space. This approach could prove useful for the study of the in vivo operation of muscarinic and, by extension, a number of receptors coupled to phosphoinositide turnover. 相似文献
16.
Anti-Candida activity of four antifungal benzothiazoles 总被引:1,自引:0,他引:1
Helena Bujdáková Tomá Kuchta Eva Sidóová Anna Gvozdjaková 《FEMS microbiology letters》1993,112(3):329-334
Abstract Anti- Candida activity of 6-amino-2- n -pentylthiobenzothiazole (I), benzylester of (6-amino-2-benzothiazolylthio)acetic acid (II) and of 3-butylthio-(1,2,4-triazolo)-2,3-benzothiazole (III) was followed and compared to that of 2-mercaptobenzothiazole (IV). I and II exhibited good activity against the C. albicans yeast form, similar to IV. They were inhibitorily active against other Candida strains, IC50 values being of the order of 10−5 M, which means better activity than IV. Compound I also exhibited inhibitory activity on germ-tube formation and mycelial growth in the C. albicans strains, while II, III and IV were not active in these tests. III was the least active form of the compounds tested, IC50 values being of the order of 10−4 M. All the compounds tested were highly active on a nystatin-resistant C. albicans mutant, with IC50 s of the order of 10−6 M−10−5 M. 相似文献
17.
Effects of flooding under hydrostatic pressure on the respiratory metabolism of germinated wheat seeds 总被引:1,自引:0,他引:1
Germinated wheat seeds ( Triticum aestivum L. cv. Barqai) that had been subjected to short hydrostatic pressure treatments (0.3–1.2 MPa) changed their normal metabolism into one which is characterized by a high ethanol production, a low O2 consumption and a low CO2 evolution. Alcoholic fermentation could account for ca half of the CO2 evolved from the pressurized seeds. The level of acetaldehyde was low, though significantly higher in the pressurized seeds than in the controls. Subjection of wheat seeds to osmotic stress under aerobic conditions lowered their O2 uptake and CO2 evolution but did not induce ethanol production. Exposure of pressurized seeds to NaCl stress did not alter their ethanol production beyond that which had been induced by pressure. Ethanol production by pressurized seeds increased following either the addition of sucrose or by excision of the embryos from the endosperms. More electrolytes leaked into the embedding solution from pressurized seeds than from control seeds. Exogenous ethanol was toxic to wheat seeds at concentrations as low as 343 m M . The effects of hydrostatic pressure and of the consequently induced ethanol production on the mortality of flooded seeds is discussed. 相似文献
18.
Di- n -butyl phthalate (DBF) is widely used as a plasticizer and has been found in all types of ecosystems. It inhibits growth and photosynthesis of green algae ( Chlorella emersonii CCAP strain 211/8 h and Selenastrum capricornutum CCAP strain 278/4) at concentrations higher than 10-5 M . The IC50 value for CO2 -dependent oxygen evolution in algae was 3 × 10-4 M. The CO2 -reduction in isolated protoplasts prepared from barley ( Hordeum vulgare L. cv. Simba) was also inhibited by phthalate. The IC50 value was 2 × 10-4 M . The electron transport in isolated thylakoids prepared from spinach was inhibited with an IC50 value of 3 × 10-4 M . The IC50 value for uncoupled electron transport extrapolated to zero chlorophyll concentration was 2.5 × 10-5 M . The effect of di-n-butyl phthalate was localized to reactions in photosystem II. Di-n-butyl phthalate could thus be a pollutant which affects growth and photosynthesis of plants. The reported IC50 values may be underestimated since di- n -butyl phthalate can attach to surfaces. The results are discussed in relation to observed effects of di- n -butyl phthalate on other organisms. 相似文献
19.
Tomoya Yoshinari Atsushi Yaguchi Naoko Takahashi-Ando Makoto Kimura Haruo Takahashi Takashi Nakajima Yoshiko Sugita-Konishi Hiromichi Nagasawa & Shohei Sakuda 《FEMS microbiology letters》2008,284(2):184-190
The essential oil of German chamomile showed specific inhibition toward aflatoxin G1 (AFG1 ) production, and ( E )- and ( Z )-spiroethers were isolated as the active compounds from the oil. The ( E )- and ( Z )-spiroethers inhibited AFG1 production of Aspergillus parasiticus with inhibitory concentration 50% (IC50 ) values of 2.8 and 20.8 μM, respectively, without inhibiting fungal growth. Results of an O- methylsterigmatocystin (OMST) conversion study indicated that the spiroethers specifically inhibited the OMST to AFG1 pathway. A cytochrome P450 monooxygenase, CYPA, is known as an essential enzyme for this pathway. Because CYPA has homology with TRI4, a key enzyme catalyzing early steps in the biosynthesis of trichothecenes, the inhibitory actions of the two spiroethers against TRI4 reactions and 3-acetyldeoxynivalenol (3-ADON) production were tested. ( E ) - and ( Z ) - spiroethers inhibited the enzymatic activity of TRI4 dose-dependently and interfered with 3-ADON production by Fusarium graminearum , with IC50 values of 27.1 and 103 μM, respectively. Our results suggest that the spiroethers inhibited AFG1 and 3-ADON production by inhibiting CYPA and TRI4, respectively. 相似文献
20.
Dean C. Crick Julie Suders Catherine M. Kluthe Douglas A. Andres Charles J. Waechter 《Journal of neurochemistry》1995,65(3):1365-1373
Abstract: The effect of squalestatin 1 (SQ) on squalene synthase and other enzymes utilizing farnesyl pyrophosphate (F-P-P) as substrate was evaluated by in vitro enzymological and in vivo metabolic labeling experiments to determine if the drug selectively inhibited cholesterol biosynthesis in brain cells. Direct in vitro enzyme studies with membrane fractions from primary cultures of embryonic rat brain (IC50 = 37 n M ), pig brain (IC50 = 21 n M ), and C6 glioma cells (IC50 = 35 n M ) demonstrated that SQ potently inhibited squalene synthase activity but had no effect on the long-chain cis -isoprenyltransferase catalyzing the conversion of F-P-P to polyprenyl pyrophosphate (Poly-P-P), the precursor of dolichyl phosphate (Dol-P). SQ also had no effect on F-P-P synthase; the conversion of [3 H]F-P-P to geranylgeranyl pyrophosphate (GG-P-P) catalyzed by partially purified GG-P-P synthase from bovine brain; the enzymatic farnesylation of recombinant H-p21 ras by rat brain farnesyltransferase; or the enzymatic geranylgeranylation of recombinant Rab1A, catalyzed by rat brain geranylgeranyltransferase. Consistent with SQ selectively blocking the synthesis of squalene, when C6 glial cells were metabolically labeled with [3 H]mevalonolactone, the drug inhibited the incorporation of the labeled precursor into squalene and cholesterol (IC50 = 3–5 µ M ) but either had no effect or slightly stimulated the labeling of Dol-P, ubiquinone (CoQ), and isoprenylated proteins. These results indicate that SQ blocks cholesterol biosynthesis in brain cells by selectively inhibiting squalene synthase. Thus, SQ provides a useful tool for evaluating the obligatory requirement for de novo cholesterol biosynthesis in neurobiological processes without interfering with other critical reactions involving F-P-P. 相似文献