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1.
Curr Pharm Des ; 12(8): 963-9, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16533163

RESUMEN

We have chemically synthesized several stable analogs of the naturally occurring hepoxilins, 12-LO products derived from arachidonic acid, which we found to have promising actions in a variety of test systems of disease. The analogs, PBTs, afford chemical and biological stability to the hepoxilin molecule. This article reviews some of our latest observations with the PBTs in the areas of inflammation (inhibition of the bleomycin-evoked lung fibrosis in mice in vivo), platelet aggregation (antagonism of the thromboxane receptor in human platelets in vitro) and thrombosis (inhibitors in vivo), and cancer (apoptosis of the human leukemia cell line, K562 in vitro and in vivo). The demonstration that the PBTs are active in vivo suggests that they can serve as a platform for their further development as novel therapeutics in disease.


Asunto(s)
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Fibrinolíticos/farmacología , Ácido 8,11,14-Eicosatrienoico/farmacología , Ácido 8,11,14-Eicosatrienoico/uso terapéutico , Animales , Antiinflamatorios/uso terapéutico , Apoptosis/efectos de los fármacos , Bleomicina , Plaquetas/efectos de los fármacos , Modelos Animales de Enfermedad , Humanos , Células K562 , Leucemia Experimental/tratamiento farmacológico , Pulmón/efectos de los fármacos , Pulmón/patología , Ratones , Agregación Plaquetaria/efectos de los fármacos , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/prevención & control
2.
Med Tekh ; (6): 23-4, 2002.
Artículo en Ruso | MEDLINE | ID: mdl-12506743

RESUMEN

The paper deals with the use of multichannel programmed electrostimulation of muscles or artificial correction of movements to treat patients with infantile cerebral paralysis. This electrostimulation is a highly effective technique for correction of a pathological human motor stereotype and serves to consolidate the physiological movement patterns simulated during treatment sessions.


Asunto(s)
Parálisis Cerebral/rehabilitación , Terapia por Estimulación Eléctrica , Marcha/fisiología , Movimiento/fisiología , Músculo Esquelético/fisiología , Parálisis Cerebral/fisiopatología , Niño , Humanos , Músculo Esquelético/fisiopatología , Modalidades de Fisioterapia
3.
J Chromatogr B Biomed Sci Appl ; 762(2): 175-80, 2001 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-11678377

RESUMEN

We report herein an improved method for the high-performance liquid chromatographic separation and analysis of eicosanoids formed during the stimulation of human platelets in vitro with collagen. Since the products of interest, excepting arachidonic acid, contain hydroxyl groups (one to several), our method involves the conversion of the hydroxyl groups into acetates (pyridine/acetic anhydride) after derivatization with anthryl diazomethane (ADAM) rendering the compounds with much decreased polarity for separation on a reversed-phase column. This procedure is superior to that involving ADAM esters only, i.e. with free hydroxyl groups, as it leads to the excellent separation of the desired compounds from each other and from extraneous peaks observed due to the ADAM reagent and sharpens the peak of thromboxane. We have successfully applied the method to investigate the formation of thromboxane B2 and 12-hydroxyheptadecatrienoic acid (HHT) (products of cyclooxygenase and thromboxane A2 synthase), 12-hydroxyeicosatetraenoic acid (12-HETE, a 12-lipoxygenase product) and arachidonic acid (AA, product of phospholipase A2) formed during the in vitro aggregation of human platelets induced by collagen. A correlation between the inhibition of aggregation by aspirin and thromboxane/HHT formation was observed. All four compounds can be chromatographed in a single run. We employed prostaglandin B1 (PGB1) as internal reference standard to quantify the products. The method is useful to investigate selectivity of drugs which may affect either or all of these enzyme pathways at the same time.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Lipooxigenasa/sangre , Fosfolipasas/sangre , Prostaglandina-Endoperóxido Sintasas/sangre , Plaquetas/enzimología , Humanos , Estándares de Referencia
4.
Biochem Biophys Res Commun ; 284(3): 580-2, 2001 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-11396939

RESUMEN

We describe herein a novel action of four stable analogs of the hepoxilins. These analogs inhibit to different degrees, the aggregation of washed human platelets evoked by collagen. One of the analogs, PBT-3, is particularly effective with an IC(50) = 8 x 10(-7) M. The other analogs are about 5-fold less active, but all analogs are about 500-fold more active than the native hepoxilins. The PBT analogs inhibit the collagen-enhanced formation of thromboxane A(2) and HHT but do not affect the formation of 12-HETE or the release of arachidonic acid except at doses higher than those needed to block platelet aggregation. These results demonstrate that these novel compounds may have potential for development into drugs in the treatment of thromboxane-mediated cardiovascular disease.


Asunto(s)
Ácidos Hidroxieicosatetraenoicos/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Ácidos Araquidónicos/biosíntesis , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Células Cultivadas , Colágeno/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Tromboxanos/biosíntesis
5.
Gen Pharmacol ; 33(5): 377-82, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10553878

RESUMEN

Native hepoxilins (Hx) A3 and B3 as well as their synthetic cyclopropane analogs, HxdeltaA3 and HxdeltaB3 are inactive on their own in causing changes in vascular permeability in rat skin measured by leakage of plasma-bound Evans Blue dye. Several of these compounds, however, were observed to potentiate the leakage of dye evoked by bradykinin (BK) and platelet-activating factor (PAF). The syn epimer of HxA3 was effective in potentiating dye leakage evoked by BK but not by PAF. The syn epimer of HxB3, on the other hand, was capable of potentiating both BK- and PAF-evoked plasma protein leakage. The anti epimer of both hepoxilins was inactive. In contrast, the anti epimer of the cyclopropane analog HxdeltaA3 potentiated only the BK-evoked changes, whereas the anti epimer of HxdeltaB3 potentiated only the PAF-evoked changes in dye leakage. The corresponding other epimer of each compound was inactive. Our findings indicate that the hepoxilin cyclopropane analogs appear to mimic the actions of the native compounds.


Asunto(s)
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Permeabilidad Capilar/efectos de los fármacos , Ciclopropanos/farmacología , Piel/efectos de los fármacos , Ácido 8,11,14-Eicosatrienoico/farmacología , Administración Cutánea , Animales , Bradiquinina/farmacología , Sinergismo Farmacológico , Masculino , Factor de Activación Plaquetaria/farmacología , Ratas , Ratas Wistar , Piel/irrigación sanguínea , Estereoisomerismo
6.
FEBS Lett ; 461(3): 165-8, 1999 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-10567690

RESUMEN

We have demonstrated over a decade ago that hepoxilins cause the release of insulin from isolated pancreatic islets of Langerhans in vitro. However, no studies are available so far to indicate whether these compounds are active in vivo. The present study is the first to our knowledge which demonstrates that hepoxilins administered intra-arterially in the anaesthetized rat cause the release of insulin in the circulation. This release is dependent on the glucose status of the rat. Hence, animals fasted overnight do not respond to hepoxilin administration, while animals that have had free access to food respond to hepoxilins with a rise in insulin concentrations in blood. The hepoxilin effect is rapid and varies with different hepoxilins, the most potent of which is hepoxilin A(3) (HxA(3)) (both the 8S and the 8R enantiomers). Administration of 100 microg HxA(3) produces a rise in blood insulin equivalent to that caused by the administration of 5 mg glucose. In view of earlier evidence showing that these compounds cause a rise in intracellular calcium levels in vitro at a <1 microg/ml concentration through a receptor-mediated mechanism, we speculate that the actions of hepoxilins in causing the release of insulin from the pancreas may be due to alterations in calcium levels within the beta-cell. We believe that hepoxilins may represent new lead compounds as therapeutics in type II diabetes mellitus.


Asunto(s)
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Insulina/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Ácido 8,11,14-Eicosatrienoico/farmacología , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diseño de Fármacos , Insulina/sangre , Secreción de Insulina , Islotes Pancreáticos/metabolismo , Masculino , Ratas , Ratas Wistar , Tasa de Secreción/efectos de los fármacos , Estimulación Química
7.
J Biol Chem ; 274(40): 28213-8, 1999 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-10497175

RESUMEN

We report herein for the first time the formation by freshly grown garlic roots and the structural characterization of 14,15-epoxide positional analogs of the hepoxilins formed via the 15-lipoxygenase-induced oxygenation of arachidonic acid. These compounds are formed through the combined actions of a 15(S)-lipoxygenase and a hydroperoxyeicosatetraenoic acid (HPETE) isomerase. The compounds were formed when either arachidonic acid or 15-HPETE were used as substrates. Both the "A"-type and the "B"-type products are formed although the B-type compounds are formed in greater relative quantities. Chiral phase high performance liquid chromatography analysis confirmed the formation of hepoxilins from 15(S)- but not 15(R)-HPETE, indicating high stereoselectivity of the isomerase. Additionally, the lipoxygenase was of the 15(S)-type as only 15(S)-hydroxyeicosatetraenoic acid was formed when arachidonic acid was used as substrate. The structures of the products were confirmed by gas chromatography-mass spectrometry of the methyl ester trimethylsilyl ether derivatives as well as after characteristic epoxide ring opening catalytically with hydrogen leading to dihydroxy products. That 15(S)-lipoxygenase activity is of functional importance in garlic was shown by the inhibition of root growth by BW 755C, a dual cyclooxygenase/lipoxygenase inhibitor and nordihydroguaiaretic acid, a lipoxygenase inhibitor. Additional biological studies were carried out with the purified intact 14(S), 15(S)-hepoxilins, which were investigated for hepoxilin-like actions in causing the release of intracellular calcium in human neutrophils. The 14,15-hepoxilins dose-dependently caused a rise in cytosolic calcium, but their actions were 5-10-fold less active than 11(S), 12(S)-hepoxilins derived from 12(S)-HPETE. These studies provide evidence that 15(S)-lipoxygenase is functionally important to normal root growth and that HPETE isomerization into the hepoxilin-like structure may be ubiquitous; the hepoxilin-evoked release of calcium in human neutrophils, which is receptor-mediated, is sensitive to the location within the molecule of the hydroxyepoxide functionality.


Asunto(s)
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Araquidonato 15-Lipooxigenasa/metabolismo , Ajo/enzimología , Oxidorreductasas Intramoleculares/metabolismo , Plantas Medicinales , Ácido 8,11,14-Eicosatrienoico/metabolismo , Cromatografía Líquida de Alta Presión , Humanos , Neutrófilos/metabolismo , Raíces de Plantas/enzimología , Receptores de Superficie Celular/metabolismo
8.
FEBS Lett ; 446(2-3): 236-8, 1999 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-10100848

RESUMEN

We have previously shown that the methyl ester of hepoxilin A3 causes a receptor-induced rise in intracellular calcium through the release from intracellular stores in suspended human neutrophils. The corresponding free acid was devoid of activity. We now report that the action of the free acid form of hepoxilin A3 is dependent on the type of vehicle used, i.e. it is active in releasing calcium when used in an ethanol vehicle but not in DMSO. The methyl ester is equally active in either vehicle. The pattern of calcium release between the free acid and the methyl ester is qualitatively different. Both compounds show a biphasic pattern, i.e. an initial rapid phase followed by a slow decline in calcium levels but never reaching pre-hepoxilin A3 baseline levels. The methyl ester appears slightly more potent in the initial phase of calcium release than the free acid (methyl = 188+/-14 S.D., free acid = 135+/-11 S.D. nM, P < 0.0005). Both compounds appear to reach the same calcium levels at the plateau of the second prolonged phase (methyl = 88+/-8 S.D., free acid = 107+/-15 S.D. nM, not significant). Lanthanum chloride (an inhibitor of calcium influx) interfered with the second phase of the curve causing calcium levels to return to normal pre-hepoxilin levels for both compounds. Addition of lanthanum chloride prior to the hepoxilin addition or carrying out the experiments in calcium-free medium, eliminated the second phase completely, with the calcium peak returning rapidly to normal baseline levels, suggesting that the second phase is due to calcium influx. Again the methyl ester is more active than the free acid (methyl, 189+/-12; free acid, 145+/-6 S.D. nM, P<0.005). Additional experiments with tritium-labelled methyl ester of hepoxilin A3 demonstrated that the compound is hydrolyzed into the free acid intracellularly. These experiments demonstrate that DMSO interacts with hepoxilin free acid, interfering with its entry into the cell while ethanol does not. Once inside the cell, hepoxilin interacts with its own receptor to release calcium rapidly from stores, but it also causes a more prolonged influx of calcium from the extracellular milieu.


Asunto(s)
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Calcio/metabolismo , Neutrófilos/metabolismo , Transducción de Señal , Ácido 8,11,14-Eicosatrienoico/metabolismo , Células Cultivadas , Esterificación , Humanos , Líquido Intracelular/metabolismo
9.
Adv Exp Med Biol ; 447: 123-32, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10086189

RESUMEN

This manuscript reviews the literature on hepoxilins to date. It affords a review of the structures, nomenclature, biosynthesis, catabolism and biological actions of the hepoxilins and some of their chemical analogs. Some unpublished data are also presented. The primary biological action of the hepoxilins appears to relate to their ability to release calcium from intracellular stores through a receptor-mediated action. The receptor is intracellular, and appears to be G-protein coupled. The conversion of hepoxilin into its omega-hydroxy catabolite has recently been demonstrated through the action of an omega-hydroxylase. This enzyme is different from that which oxidizes leukotriene B4, as the former activity is lost when the cell is disrupted, while leukotriene B4-catabolic activity is recovered in both the intact and disrupted cell. Additionally, hepoxilin catabolism is inhibited by CCCP, a mitochondrial uncoupler, while leukotriene catabolism is unaffected. As hepoxilins cause the translocation of calcium from intracellular stores in the endoplasmic reticulum to the mitochondria, it is speculated that hepoxilin omega-oxidation takes place in the mitochondria, and the omega-oxidation product facilitates accumulation of the elevated cytosolic calcium by the mitochondria. The biological activity of stable analogs of the hepoxilins is also described which inhibit the calcium-releasing actions of neutrophil inflammatory mediators.


Asunto(s)
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/química , Ácido 8,11,14-Eicosatrienoico/clasificación , Ácido 8,11,14-Eicosatrienoico/metabolismo , Humanos , Receptores de Superficie Celular/metabolismo
11.
Biochim Biophys Acta ; 1348(3): 287-98, 1997 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-9366245

RESUMEN

Hepoxilin A3-methyl ester is taken up by intact human neutrophils where it is first hydrolyzed into the free acid which is subsequently converted into a single major metabolite. The structure of this metabolite was determined through mass spectral analysis of several derivatives, and through identity with an authentic compound prepared by chemical synthesis. The metabolite was identified as omega-hydroxy-hepoxilin A3 showing that the epoxide functionality of the parent hepoxilin is not opened during incubation with human neutrophils. All attempts to investigate hepoxilin metabolism in broken cells, despite the presence of protease inhibitors (Aproteinin, PMSF, DFP) and supplementation with NADPH were unsuccessful. Metabolism of hepoxilin A3 required the intact cell, while parallel experiments with LTB4 as substrate demonstrated that this eicosanoid was metabolized into its omega-hydroxy metabolite regardless of whether intact or broken cell preparations were used provided that NADPH was present in the latter. Hepoxilin metabolism in intact cells was inhibited dose-dependently by CCCP (0.01-100 microM), a mitochondrial uncoupler, whereas LTB4 metabolism was unaffected by CCCP. This data suggests that metabolism of hepoxilin A3 occurs in intact human neutrophils through omega-oxidation, is likely located in the mitochondrial compartment of the cell (inhibition by CCCP) and is carried out by an activity that is independent of the well characterized, relatively stable microsomal LTB4 omega-hydroxylase.


Asunto(s)
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Sistema Enzimático del Citocromo P-450/metabolismo , Oxigenasas de Función Mixta/metabolismo , Neutrófilos/enzimología , Ácido 8,11,14-Eicosatrienoico/química , Ácido 8,11,14-Eicosatrienoico/metabolismo , Adenosina Trifosfato/farmacología , Carbonil Cianuro m-Clorofenil Hidrazona/farmacología , Cromatografía en Capa Delgada , Familia 4 del Citocromo P450 , Cromatografía de Gases y Espectrometría de Masas , Humanos , Hidrólisis , Leucotrieno B4/metabolismo , NAD/farmacología , NADP/metabolismo , NADP/farmacología , Oxidación-Reducción
13.
J Lipid Mediat Cell Signal ; 13(1): 63-72, 1996 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8998598

RESUMEN

A novel analog of hepoxilin A3 has been chemically synthesized in which the 11,12-epoxide group has been altered to a thiirano group. This has been accomplished through allylic rearrangement of unnatural (11 R, 12 R)-hepoxilin B3 under Mitsunobu conditions, first into unnatural (11 R, 12 R)-hepoxilin A3, followed by conversion of this compound with inversion of the epoxide centers into the thiirano-hepoxilin A3 having the natural 11 S, 12 S configuration. We also report herein evidence showing that thiirano-hepoxilin A3 raises intracellular calcium concentrations in intact human neutrophils.


Asunto(s)
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Calcio/metabolismo , Neutrófilos/efectos de los fármacos , Ácido 8,11,14-Eicosatrienoico/síntesis química , Ácido 8,11,14-Eicosatrienoico/química , Ácido 8,11,14-Eicosatrienoico/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Espectroscopía de Resonancia Magnética , Conformación Molecular , Neutrófilos/metabolismo
14.
Biochem J ; 313 ( Pt 2): 537-41, 1996 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-8573089

RESUMEN

Hepoxilins have been shown to release calcium from intracellular stores in human neutrophils [Dho, Grinstein, Corey, Su and Pace-Asciak (1990) Biochem. J. 266, 63-68; Laneuville, Reynaud, Grinstein, Nigam and Pace-Asciak (1993) Biochem. J. 295, 393-397]. In this paper we report that tritium-labelled hepoxilin A3 (8S) binds to broken neutrophil membranes in a time-, substrate- and temperature-dependent fashion. Specific binding was displaced with unlabelled hepoxilin A3. Specific binding was greatest at 37 degrees C. Competitive binding was best observed with unlabelled hepoxilin A3 (8S); the glutathione conjugate, HxA3-C (8S or 8R), or 12(S)-hydroxyeicosatetraenoic acid was less active. Similarly inactive in displacing the bound radiolabelled hepoxilin A3 was leukotriene B4 as well as a variety of prostaglandins and thromboxane B2. Formylmethionyl-leucylphenylalanine was similarly inactive in competing for the hepoxilin binding sites. Specific binding was inhibited by pretreatment of the broken membranes during 30 min at 37 degrees C with proteinase K, while specific binding of the intact cells was unaffected. Scatchard analysis of binding data revealed a single population of binding sites with apparent KD and Bmax. of 79.3 +/- 9.1 nM and 8.86 +/- 1.4 pmol/ml per 2 x 10(6) cells (+/- S.E.M.) respectively reflecting approx. 2.67 x 10(6) sites/cell. These results demonstrate for the first time that neutrophils contain specific binding sites to hepoxilin A3.


Asunto(s)
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Neutrófilos/metabolismo , Ácido 8,11,14-Eicosatrienoico/metabolismo , Sitios de Unión , Endopeptidasa K , Humanos , Hidrólisis , Cinética , Serina Endopeptidasas/metabolismo , Tritio
15.
J Chromatogr B Biomed Appl ; 672(2): 282-9, 1995 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-8581135

RESUMEN

Fluorescent anthryl (ADAM) derivatives of hepoxilins have been shown to possess good chromatographic properties affording good sensitivity for the high-performance liquid chromatographic analysis and detection of these compounds and related eicosanoids (12-hydroxyeicosatetraenoic acid) in biological samples. We report herein the separation of all possible stereoisomers of hepoxilins A3 and B3 as their methyl esters as well as their ADAM ester and acetate derivatives on a cellulose trisdimethyphenylcarbamate chiral stationary phase (Chiracel OD) in the normal-phase mode. This methodology is important to address the mechanistic route of biosynthesis of these products.


Asunto(s)
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Cromatografía Líquida de Alta Presión/métodos , Colorantes Fluorescentes , Ácido 8,11,14-Eicosatrienoico/química , Ácido 8,11,14-Eicosatrienoico/aislamiento & purificación , Acetatos , Antracenos , Cromatografía Líquida de Alta Presión/estadística & datos numéricos , Ésteres , Estereoisomerismo
17.
Anal Biochem ; 226(2): 252-5, 1995 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-7793626

RESUMEN

Facile methods for the detection of intact hepoxilins, monohydroxy-epoxide derivatives of arachidonic acid formed through the 12-lipoxygenase pathway, are unavailable because (i) an absence in these compounds of an appropriate chromophore for sensitive detection by uv exists, (ii) these compounds are sensitive to the acidic workup leading to varying degrees of decomposition, and (iii) they decompose to the derivatization procedures required for their analysis by gas chromatography mass spectrometry. Herein we apply a method which introduces a fluorescent ester chromophore to the carboxylic group of the hepoxilins under conditions which do not require acidification leading to stabilization of the derivative which is extracted into an organic solvent in situ. This procedure quantitatively derivatizes hepoxilins in a biological sample, permitting the detection of hepoxilins after a TLC purification with a limit of 50 pg/sample. This method permits the profiling of 12-HETE, hepoxilins A3 and B3, as well as the corresponding epoxide hydrolase products, trioxilins A3 and B3, in a biological sample by reverse-phase HPLC with fluorescent detection. We also report on the fluorescent and mass spectral properties of these derivatives using a liquid chromatography mass spectrometry LCMS interface with thermospray ionization.


Asunto(s)
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Cromatografía Líquida de Alta Presión/métodos , Eicosanoides/análisis , Ácidos Hidroxieicosatetraenoicos/análisis , Lipooxigenasa/metabolismo , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico , Ácido 8,11,14-Eicosatrienoico/análisis , Animales , Antracenos/metabolismo , Ácido Araquidónico/metabolismo , Ésteres , Glándula Pineal/química , Ratas , Espectrometría de Fluorescencia/métodos
18.
Biochem Biophys Res Commun ; 207(1): 191-4, 1995 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-7857263

RESUMEN

Hepoxilins have previously been shown to release intracellular calcium in human neutrophils. We show herein that tritium-labeled hepoxilin A3 of high specific radioactivity binds to human neutrophils, and this binding is reversed by the addition of unlabeled compound, demonstrating that specific binding for these compounds exists in these cells. Specific binding of both the methyl ester derivative as well as the free acid form of the hepoxilin takes place in broken membrane fragments. In contrast only the methyl ester derivative binds specifically to the intact cells. We also show that intact neutrophils form hepoxilin A3 when incubated in the presence of the hepoxilin precursor, 12(S)-HPETE. These data demonstrate that hepoxilin synthesis can occur in the neutrophil and that hepoxilin binding sites, which appear to be located intracellularly, exist in these cells.


Asunto(s)
Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Neutrófilos/metabolismo , Ácido 8,11,14-Eicosatrienoico/sangre , Análisis de Varianza , Sitios de Unión , Membrana Celular/metabolismo , Humanos , Técnicas In Vitro , Cinética , Leucotrienos/sangre , Valores de Referencia , Tritio
19.
Lipids ; 30(2): 107-14, 1995 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-7769965

RESUMEN

This article reviews published evidence describing the enzymatic and nonenzymatic formation and the routes of metabolism of the hepoxilins. Also treated are the major approaches used for the chemical synthesis of these compounds and for some of their analogs.


Asunto(s)
Leucotrienos/metabolismo , Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/síntesis química , Ácido 8,11,14-Eicosatrienoico/metabolismo , Animales , Estabilidad de Medicamentos , Leucotrienos/síntesis química , Estructura Molecular
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