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151.
Xavier Khawaja Non Evans Yvonne Reilly Christine Ennis Michael C. W. Minchin 《Journal of neurochemistry》1995,64(6):2716-2726
Abstract: The specific binding of [3H]WAY-100635 {N-[2-[4-(2-[O-methyl-3H]methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexane carboxamide trihydrochloride} to rat hippocampal membrane preparations was time, temperature, and tissue concentration dependent. The rates of [3H]WAY-100635 association (k+1 = 0.069 ± 0.015 nM?1 min?1) and dissociation (k?1 = 0.023 ± 0.001 min?1) followed monoexponential kinetics. Saturation binding isotherms of [3H]WAY-100635 exhibited a single class of recognition site with an affinity of 0.37 ± 0.051 nM and a maximal binding capacity (Bmax) of 312 ± 12 fmol/mg of protein. The maximal number of binding sites labelled by [3H]WAY-100635 was ~36% higher compared with that of 8-hydroxy-2-(di-n-[3H]-propylamino)tetralin ([3H]8-OH-DPAT). The binding affinity of [3H]WAY-100635 was significantly lowered by the divalent cations CaCl2 (2.5-fold; p < 0.02) and MnCl2 (3.6-fold; p < 0.05), with no effect on Bmax. Guanyl nucleotides failed to influence the KD and Bmax parameters of [3H]WAY-100635 binding to 5-HT1A receptors. The pharmacological binding profile of [3H]WAY-100635 was closely correlated with that of [3H]8-OH-DPAT, which is consistent with the labelling of 5-hydroxytryptamine1A (5-HT1A) sites in rat hippocampus. [3H]WAY-100635 competition curves with 5-HT1A agonists and partial agonists were best resolved into high- and low-affinity binding components, whereas antagonists were best described by a one-site binding model. In the presence of 50 µM guanosine 5′-O-(3-thiotriphosphate) (GTPγS), competition curves for the antagonists remained unaltered, whereas the agonist and partial agonist curves were shifted to the right, reflecting an influence of G protein coupling on agonist versus antagonist binding to the 5-HT1A receptor. However, a residual (16 ± 2%) high-affinity agonist binding component was still apparent in the presence of GTPγS, indicating the existence of GTP-insensitive sites. 相似文献
152.
153.
Christine Heberden Thierry Mercier Isabelle Gaillard-Sanchez Brigitte Huet Paule Martel 《Experimental cell research》1995,218(2)
We assessed the presence and the role of membrane TGF-α in two rat liver epithelial cell lines, either parental or transfected with c-fos proto-oncogene. c-fos overexpressing cells had more TGF-α-like activity in their membranes. When TGF-α was removed by elastase or neutralized, the growth rates of both cell lines were markedly reduced, but to a higher extent for parental cells. If membrane TGF-α seemed to play a key contribution in normal cell growth, both cell lines were unable to react to the addition of soluble TGF-α, showing that these two forms of growth factors are not equivalent. 相似文献
154.
Susan J. Holt Peter Alexander Chris B. Inman Donna E. Davies 《Experimental cell research》1995,217(2)
Ligand-induced translocation of epidermal growth factor receptors (EGF-R) to the nucleus of NR6/HER fibroblasts has been studied by immunoelectron microscopy. Following treatment of NR6/HER cells with epidermal growth factor (EGF) for 1 h, there was a decrease in EGF-R labeling at the plasma membrane and a corresponding increase in EGF-R in the nucleus. This was preceded by a rapid and sustained increase in nuclear phosphotyrosine content, detectable within 2 min of EGF treatment. EGF-R translocation into the nucleus was completely prevented by 18 h serum starvation prior to treatment with EGF. These results indicate that translocation of EGF-R to the nucleus is a controlled process and they suggest theft EGF-R may directly influence nuclear function. 相似文献
155.
Ioannis Dragatsis Christine Zioudrou Kyriaki Gerozissis 《Cellular and molecular neurobiology》1995,15(4):389-400
Summary 1. Inin vitro studies with adult male rats we have recently shown that the delta-opioid agonist DTLET inhibits the release of the Gonadotropin-Releasing Hormone (GnRH) from hypothalamic fragments containing the arcuate nucleus and the median eminence. This effect is receptor mediated and eicosanoid dependent (Gerozissiset al., 1993).2. In the present study we report that the delta-opioid antagonists with negative intrinsic activity, Diallyl-G and ICI 174864, applied under the same experimental conditions (30 min static incubations at 37°C, in a potassium rich milieu), in the absence of the agonist DTLET, also exert a similar to the agonist inhibitory effect on the release of GnRH.3. The dose-dependent inhibitory effect of Diallyl-G on GnRH release is reversed by increasing concentrations of DTLET. The mu and delta opioid antagonist, naloxone is without effect in the absence of DTLET. However, naloxone acts as an antagonist on the Diallyl-G-induced inhibition of GnRH release.4. Diallyl-G also inhibits the release of prostaglandin E2 (PGE2). In the presence of indomethacin or nordihydroguaiaretic acid, Diallyl-G is ineffective to further inhibit the release of GnRH. These latter observations taken together with the results of eicosanoid estimation suggest that PGE2 but not leukotrienes participate in the agonist-independent effects of Diallyl-G on GnRH release.5. Therefore these results support the hypothesis that delta-opioid antagonists with negative intrinsic activity exert agonist-independent biological responses similar to those of the agonists. 相似文献
156.
Bernard N. Violand Michael R. Schlittler Kevin L. Duffin Christine E. Smith 《Journal of Protein Chemistry》1995,14(5):341-347
The disulfide bond assignments of human alanyl tissue factor pathway inhibitor purified fromEscherichia coli have been determined. This inhibitor of the extrinsic blood coagulation pathway possesses three Kunitz-type inhibitor domains, each containing three disulfide bonds. The disulfide bond pairings in domains 1 and 3 were determined by amino acid sequencing and mass spectrometry of peptides derived from a thermolysin digest. However, thermolysin digestion did not cleave any peptide bonds within domain 2. The disulfide bond pairings in domain 2 were determined by isolating it from the thermolysin treatment and subsequently cleaving it with pepsin and trypsin into peptides which yielded the three disulfide bond pairings in this domain. These results demonstrate that the disulfide pairings in each of the three domains of human tissue factor pathway inhibitor purified fromEscherichia coli are homologous to each other and also to those in bovine pancreatic trypsin inhibitor. 相似文献
157.
Fabrice Cornille Loïc Martin Christine Lenoir Didier Cussac Bernard P. Roques Marie-Claude Fournié-Zaluski 《Letters in Peptide Science》1997,4(4-6):207-212
The light chain of tetanus neurotoxin (TeNT L chain)has been shown to be endowed with zinc endopeptidaseactivity, selectively directed towards theGln76–Phe77 bond of synaptobrevin, avesicle-associated membrane protein criticallyinvolved in neuroexocytosis. In previous reports,truncations at the NH2- and COOH-terminus ofsynaptobrevin have shown that the sequence 39–88 ofsynaptobrevin is the minimum substrate of TeNT,suggesting either the requirement of a well-definedthree-dimensional structure of synaptobrevin or a rolein the mechanism of substrate hydrolysis for residuesdistal from the cleavage site. In this study, theaddition of NH2- and COOH-terminal peptides ofsynaptobrevin, S 27–55 (S1) and S 82–93(S2), to the synaptobrevin fragment S 56–81allowed the cleavage of this latter peptide by TeNT tooccur. This appears to result from an activationprocess mediated by the simultaneous binding ofS1 and S2 with complementary sites presenton TeNT as shown by surface plasmon resonanceexperiments. All these results favor anexosite-controlled hydrolysis of synaptobrevin by TeNTprobably involving a conformational change of thetoxin. This could account for the high degree ofsubstrate specificity of TeNT and, probably, botulinumneurotoxins. 相似文献
158.
Florine Cavelier Christine Enjalbal Jérome Santolini Francis Haraux Claude Sigalat Jean Verducci François André 《Letters in Peptide Science》1997,4(4-6):283-288
Tentoxin[cyclo-(MeAla1-Leu2-MePhe3-Gly4] is a metabolite isolated from a phytopathogenic fungusAlternaria alternata, which induces chlorosis of many plants. This potentialnatural herbicide binds specifically to the soluble part CF1of the chloroplastic coupling factor, which is a proton ATP-synthase. Theeffect of the toxin is concentration dependent: at low concentration it is apowerful inhibitor, while at higher concentration, it stimulates the enzyme.We synthesized tentoxin and we designed new analogues in order to vary thehydrophobicity on the side chain and to study the structure activityrelationships. Comparative activities suggest that it is possible toseparate inhibitory and activating effects using tentoxin analogues, showingsome evidence for the existence of two binding sites with different affinityconstant. 相似文献
159.
160.
Christine K. Wagner Joan I. Morrell 《The Journal of steroid biochemistry and molecular biology》1997,61(3-6):307-314
Aromatase, the enzyme responsible for the conversion of testosterone to estradiol, is found in the rat brain and is present in regions of the preoptic area, hypothalamus, and limbic system. Gonadal steroid hormones regulate aromatase activity levels in many brain regions, but not all. Using in situ hybridization, we examined the distribution of aromatase mRNA in the adult male forebrain, as well as the levels of aromatase mRNA in the brains of males and females, and the regulation by gonadal steroid hormones. In the adult male, many heavily labelled cells were found in the encapsulated bed nucleus of the stria terminalis (BNST), the medial preoptic nucleus (MPN), the ventro-medial nucleus (VMN), the medial amygdala (mAMY) and the cortical amygdala (CoAMY). The regional distribution of aromatase mRNA was similar in males and females, but males tended to have a greater number of aromatase mRNA-expressing cells in each region compared to females. Aromatase mRNA levels in the BNST, MPN, VMN and mAMY tended to be lower in castrated males than in intact males, whereas aromatase mRNA levels were unaltered by castration in the CoAMY. Further analysis of individual cells expressing aromatase mRNA suggests that aromatase mRNA may be regulated by steroid hormones differentially in specific populations of cells in regions where enzyme activity levels are steroid-hormone-dependent. 相似文献