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Pharmacology of L-660,711 (MK-571): a novel potent and selective leukotriene D4 receptor antagonist 总被引:15,自引:0,他引:15
T R Jones R Zamboni M Belley E Champion L Charette A W Ford-Hutchinson R Frenette J Y Gauthier S Leger P Masson 《Canadian journal of physiology and pharmacology》1989,67(1):17-28
L-660,711 (3-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl) ((3-dimethyl amino-3-oxo propyl)thio)methyl)thio)propanoic acid is a potent and selective competitive inhibitor of [3H]leukotriene D4 binding in guinea pig (Ki value, 0.22 nM) and human (Ki value, 2.1 nM) lung membranes but is essentially inactive versus [3H]leukotriene C4 binding (IC50 value in guinea pig lung, 23 microM). Functionally it competitively antagonized contractions of guinea pig trachea and ileum induced by leukotriene (LT) D4 (respective pA2 values, 9.4 and 10.5) and LTE4 (respective pA2 values, 9.1 and 10.4) and contractions of human trachea induced by LTD4 (pA2 value, 8.5). L-660,711 (5.8 x 10(-8)M) antagonized contractions of guinea pig trachea induced by LTC4 in the absence (dose ratio = 28) but not in the presence of 45 mM L-serine borate (dose ratio less than 2). L-660,711 (1.9 x 10(-5)M) did not block contractions of guinea pig trachea induced by histamine, acetylcholine, 5-hydroxytryptamine, PGF2 alpha, U-44069, or PGD2. In the presence of atropine, mepyramine, and indomethacin, L-660,711 (1.9 x 10(-5)M) inhibited a small component of the response to antigen on guinea pig trachea but completely blocked anti-IgE-induced contractions of human trachea. L-660,711 (i.v.) antagonized bronchoconstriction induced in anesthetized guinea pigs by i.v. LTC4, LTD4, and LTE4 but did not block bronchoconstriction to arachidonic acid, U-44069, 5-hydroxytryptamine, histamine, or acetylcholine. Intraduodenal L-660,711 antagonized LTD4 (0.2-12.8 micrograms/kg)-induced bronchoconstriction in guinea pigs, and p.o. L-660,711 blocked LTD4- and Ascaris-induced bronchoconstriction in conscious squirrel monkeys and ovalbumin-induced bronchoconstriction in conscious sensitized rats treated with methysergide (3 micrograms/kg). The pharmacological profile of L-660,711 indicates that it is a potent, selective, orally active leukotriene receptor antagonist which is well suited to determine the role played by LTD4 and LTE4 in asthma and other pathophysiologic conditions. 相似文献
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Antonella Angiolillo Fausto Panara Gina Piccinini Gian Luigi Gianfranceschi 《Molecular biology reports》1991,15(1):39-43
A protein kinase, type NII, has been purified from wheat germ chromatin. The enzyme, which uses both ATP and GTP as phosphoryl donors, catalyzes the phosphorylation of casein, phosvitin and E. coli RNA polymerase, but not of histone proteins. Polypeptide bands at 46 kDa, 37 kDa and 25 kDa were estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autophosphorylation of the 25 kDa subunit was observed following incubation of the purified kinase with (-32P)ATP and (-32P)GTP. 相似文献
5.
J. Evans R. Zamboni D. Nathaniel C. Leveill A. W. Ford-Hutchinson 《Prostaglandins & other lipid mediators》1985,30(6):981-988
The effect of micropuncture of the renal papilla through an intact ureter on urinary concetrating ability of rats was examined. Micropuncture of the renal papilla caused a fall in urine osmolality in the punctured kidney from 1718 ± 106 to 1035 ± 79 mosmol/kg·H2O. In order to investigate the role of renal prostaglandins in this process, PGE2 excretion was measured and found to increase from 63.4 ± 14.0 to 205.5 ± 57.1 pg/min. Urine osmolality and PGE2 excretion from the contralateral kidney were not significantly altered. In animals given meclofenamate (2 mg/kg·hr), renal PGE2 excretion was reduced to 22.3 ± 5.1 pg/min prior to micropuncture and it remained low at 8.9 ± 1.8pg/min after papillary micropuncture. Meclofenamate also blocked the fall in urine osmolality caused by micropuncture of the renal papilla, with urine osmolality averaging 1940 ± 122 before and 1782 ± 96 mosmol/kg·H2O after the micropuncture. These results indicated that papillary micropuncture through an intact ureter increased renal PGE2 excretion and that a rise in renal production of PGE2 or some other prostanoid is associated with a fall in urine concentrating ability. 相似文献
6.
Leukotriene B3, leukotriene B4 and leukotriene B5; binding to leukotriene B4 receptors on rat and human leukocyte membranes 总被引:1,自引:0,他引:1
S Charleson J F Evans R J Zamboni Y Leblanc B J Fitzsimmons C Leveillé P Dupuis A W Ford-Hutchinson 《Prostaglandins》1986,32(4):503-516
Specific high-affinity binding sites for [3H]-leukotriene B4 have been identified on membrane preparations from rat and human leukocytes. The rat and human leukocyte membrane preparations show linearity of binding with increasing protein concentration, saturable binding and rapid dissociation of binding by excess unlabelled leukotriene B4. Dissociation constants of 0.5 to 2.5 nM and maximum binding of 5000 fmoles/mg protein were obtained for [3H] leukotriene B4 binding to these preparations. Displacement of [3H]-leukotriene B4 by leukotriene B4 was compared with displacement by leukotriene B3 and leukotriene B5 which differ from leukotriene B4 only by the absence of a double bond at carbon 14 or the presence of an additional double bond at carbon 17, respectively. Leukotriene B3 was shown to be equipotent to leukotriene B4 in ability to displace [3H]-leukotriene B4 from both rat and human leukocyte membranes while leukotriene B5 was 20-50 fold less potent. The relative potencies for the displacement of [3H]-leukotriene B4 by leukotrienes B3, B4 and B5 on rat and human leukocyte membranes were shown to correlate well with their potencies for the induction of the aggregation of rat leukocytes and the chemokinesis of human leukocytes. 相似文献
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N Fausto 《Biochimica et biophysica acta》1969,190(1):193-201
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Summary The topographical localization of the mesangial cells in renal glomeruli of rats, and their relationships with the structures at the hilus of the glomerulus were studied in this investigation. It was observed that the mesangial cells occupy a parietal position in the wall of the glomerular capillaries, and that they are anatomically continuous with the smooth muscle cells of the tunica media of the glomerular arterioles.This study was supported by a United States Public Health Service Grant AM 08628 (Institute of Arthritis and Metabolic Diseases). 相似文献
10.
Marcella Carcupino Anna Maria Fausto Maria Luisa Bernardino Ortega Marzio Zapparoli Massimo Mazzini 《Zoomorphology》1996,116(3):103-110
Spermatophore development and ultrastructure of the mature sperm of Craterostigmus tasmanianus were studied using light and electron microscopy. In C. tasmanianus, as in the Scolopendromorpha, the spermatophore develops within the vas deferens. The latter consists of three parts, each
with a different morphology. The first may be involved in guiding the sperm to roll up into typical ring-like structures,
while the other two, which show an evident secretory activity, secrete the acellular wall of the spermatophores. The ultrastructure
of mature spermatozoa showed that a very close similarity exists between Craterostigmomorpha and Lithobiomorpha, especially
regarding the organization of the connecting piece. Based on this similarity, we consider the Craterostigmomorpha together
with the Scolopendromorpha, Geophilomorpha and Lithobiomorpha (=Pleurostigmophora) to be the sister group of the Scutigeromorpha.
Accepted: 2 June 1996 相似文献