Abstract：
:The effects of a novel nonpeptide NK1 tachykinin receptor antagonist, SR 140333, on the functional consequences of NK1 receptor activation in a human astrocytoma cell line, U373MG, were investigated. Radioligand binding conducted with 125I-Bolton-Hunter substance P revealed a competitive inhibition by SR 140333 and its R enantiomer SR 140603 with Ki values of 0.74 and 7.40 nM, respectively. The NK1-selective agonist, [Sar9,Met(O2)11]-substance P, stimulated the formation of inositol phosphates with an EC50 of 3.8 x 10(-9) M. SR 140333 blocked the stimulatory effect of this agonist (10(-7) M) with an IC50 of 1.6 x 10(-9) M, whereas the effect of another NK1 agonist, septide (EC50 = 1.5 x 10(-8) M) was antagonized with an IC50 of 2.1 x 10(-10) M. Enhancement of [3H]taurine release by [Sar9,Met(O2)11]-substance P (EC50 = 7.4 x 10(-9) M) was also inhibited by SR 140333 with an IC50 of 1.8 x 10(-9) M. SR 140603 was 10-fold less potent than SR 140333 in inhibiting inositol monophosphate formation and [3H]taurine release. The calcium mobilization induced by [Sar9,Met(O2)11]-substance P (10(-8) M) was totally prevented by 10(-8) M SR 140333. Patch-clamp experiments showed that SR 140333 depressed the outward current evoked by 5 x 10(-8) M [Sar9, Met(O2)11]-substance P with an IC50 of 1.3 x 10(-9) M. The expression of c-fos was stimulated by [Sar9,Met(O2)11]substance P with an EC50 of 2.5 x 10(-10) M, an effect that was also inhibited by SR 140333 with an IC50 of 1.1 x 10(-9) M.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Oury-Donat F,Lefevre IA,Thurneyssen O,Gauthier T,Bordey A,Feltz P,Emonds-Alt X,Le Fur G,Soubrie Pdoi
10.1046/j.1471-4159.1994.62041399.xsubject
Has Abstractpub_date
1994-04-01 00:00:00pages
1399-407issue
4eissn
0022-3042issn
1471-4159journal_volume
62pub_type
杂志文章abstract：:To evaluate the ability of ependymal, microglial and oligodendroglial cells to degrade leucine, the presence of 3-methylcrotonyl-CoA carboxylase (MCC) was investigated in cultures of these cells. MCC is a biotin-containing heterodimeric enzyme that is specific for the irreversible part of the leucine catabolic pathway...
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