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Ahmed Hasbi Jocelyne Polastron Stéphane Allouche Laura Stanasila Dominique Massotte Philippe Jauzac 《Journal of neurochemistry》1998,70(5):2129-2138
Abstract: Phosphorylation of G protein-coupled receptors is considered an important step during their desensitization. In SK-N-BE cells, recently presented as a pertinent model for the studies of the human δ-opioid receptor, pretreatment with the opioid agonist etorphine increased time-dependently the rate of phosphorylation of a 51-kDa membrane protein. Immunological characterization of this protein with an antibody, raised against the amino-terminal region of the cloned human δ-opioid receptor, revealed that it corresponded to the δ-opioid receptor. During prolonged treatment with etorphine, phosphorylation increased as early as 15 min to reach a maximum within 1 h. Phosphorylation and desensitization of adenylyl cyclase inhibition paralleled closely and okadaic acid inhibited the resensitization, a result strongly suggesting that phosphorylation of the δ-opioid receptor plays a prominent role in its rapid desensitization. The increase in phosphorylation of the δ-opioid receptor, as well as its desensitization, was not affected by H7, an inhibitor of protein kinase A and protein kinase C, but was drastically reduced by heparin or Zn2+ , known to act as G protein-coupled receptor kinase (GRK) inhibitors. These results are the first to show, on endogenously expressed human δ-opioid receptor, that a close link exists between receptor phosphorylation and agonist-promoted desensitization and that desensitization involves a GRK. 相似文献
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Seasonal dynamics of the zoobenthic communities in the mesohaline zone of the Loire estuary (France) 总被引:1,自引:1,他引:0
The application of correspondence factorial analysis to four types of sediment in the upper reaches of the Loire estuary enabled the significance of environmental factors in the spatial distribution, abundance and seasonal dynamics of the biotic communities to be determined. In coarse sand, the communities are stable but species are few in number and population densities are low. In muddy sediments (from muddy sand to fluid mud) population densities are high but undergo seasonal fluctuations due to changes in the hydrological regime (especially the dissolved oxygen regime). This is true for the composition of the biotic communities. The oligohaline phase, in which the fluvial element is predominant, is characterized by abundance maxima due to freshwater species. The mesohaline phase, in which the marine element is predominant, exerts a restrictive action on population densities; certain species are supplanted by others, their development being governed by the quality of the environment. 相似文献
5.
Contribution of Noradrenergic Neurons to the Regulation of Dopaminergic (D1 ) Receptor Denervation Supersensitivity in Rat Prefrontal Cortex 总被引:2,自引:1,他引:1
J. P. Tassin J. M. Studler D. Hervé G. Blanc J. Glowinski 《Journal of neurochemistry》1986,46(1):243-248
3,4-Dihydroxyphenylethylamine (DA, dopamine) levels in the rat prefrontal cortex were selectively decreased by 52%, leaving noradrenaline (NA) levels unaffected, 4 weeks following restricted bilateral electrolytic lesions of the ventral mesencephalic tegmentum (VMT). These lesions also induced a significant increase in DA-sensitive, but not isoproterenol-sensitive, adenylate cyclase activity in tissue homogenates (+38%). We had shown previously that chemical (6-hydroxydopamine, 6-OHDA) lesions of the VMT destroy both ascending DA and NA fibers but do not alter the D1-receptor density in the prefrontal cortex. In this study, electrolytic lesions of the VMT were combined with bilateral injections of 6-OHDA made laterally in the pedunculus cerebellaris superior to assess the role of NA fibers in the development of D1-receptor supersensitivity. This combined treatment produces a large decrease of cortical NA levels (-95%), an increase in beta-adrenergic-sensitive adenylate cyclase activity (+110%), and a decrease in DA levels (-60%), but does not alter D1-receptor density in the prefrontal cortex. These results indicate that the development of D1-receptor supersensitivity in the prefrontal cortex following electrolytic lesion of the VMT depends on the presence of an intact NA innervation. 相似文献
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Biological and physical properties of a beta-endorphin analog containing only D-amino acids in the amphiphilic helical segment 13-31 总被引:2,自引:0,他引:2
Our approach to the modeling of beta-endorphin has been based on the proposal that three basic structural units can be distinguished in the natural peptide hormone: a highly specific opiate recognition sequence at the N terminus (residues 1-5) connected via a hydrophilic link (residues 6-12) to a potential amphiphilic helix in the C-terminal residues 13-31. Our previous studies showed the validity of this approach and have demonstrated the importance of the amphiphilic helical structure in the C terminus of beta-endorphin. The present model, peptide 5, has been designed in order to evaluate further the requirements of the amphiphilic secondary structure as well as to determine the importance of this basic structural element as compared to more specific structural features which might occur in the C-terminal segment. For these reasons, peptide 5 retains the three structural units previously postulated for beta-endorphin; the major difference with regard to previous models is that the whole C-terminal segment, residues 13-31, has been built using only D-amino acids. In aqueous buffered solutions as well as in 2,2,2-trifluoroethanol-containing solutions, the CD spectra of peptide 5 show the presence of a considerable amount of left-handed helical structure. Enzymatic degradation studies employing rat brain homogenate indicate that peptide 5 is stable in this milieu. In delta- and mu-opiate receptor-binding assays, peptide 5 shows a slightly higher affinity than beta-endorphin for both receptors while retaining the same delta/mu selectivity. In opiate assays on the guinea pig ileum, the potency of peptide 5 is twice that of beta-endorphin. In the rat vas deferens assay, which is very specific for beta-endorphin, peptide 5 displays mixed agonist-antagonist activity. Most remarkably, peptide 5 displays a potent opiate analgesic effect when injected intracerebroventricularly into mice. At equal doses, the analgesic effect of peptide 5 is less than that of beta-endorphin (10-15%) but longer lasting. In conjunction with our previous model studies, these results clearly demonstrate that the amphiphilic helical structure in the C terminus of beta-endorphin is of predominant importance with regard to activity in rat vas deferens and analgesic assays. The similarity between the in vitro and in vivo opiate activities of beta-endorphin and peptide 5, when compared to the drastic change in chirality in the latter model, demonstrates that even a left-handed amphiphilic helix formed by D-amino acids can function satisfactorily as a structural unit in a beta-endorphin-like peptide. 相似文献
8.
The inhibitory effect of propionic acid P and biomass concentration X is studied in batch and continuous fermentations with cell recycle.In batch fermentations, the specific growth rate decreases and cancels out at a critical propionic acid concentration Pc
1; the formerly decreasing specific production rate becomes constant after Pc
1 and cancels out when a second critical propionic acid concentration Pc
2 is reached.In continuous fermentation with cell recycle, a similar inhibition is observed with biomass. The specific rates decrease and become constant at a critical biomass concentration Xc. They cancel out at different high biomass concentrations.In both cases, the specific production rate can be related to the specific growth rate by the Luedeking and Piret expression: =+, [1], where the constants and are determined by the fermentation parameters.List of Symbols
t h
time
-
X kg/m3
biomass concentration
-
P kg/m3
propionic acid concentration
-
A kg/m3
acetic acid concentration
-
S kg/m3
lactose concentration
- dX/dt kg/(m3h)
instantaneous rate of cell growth
- dP/dt kg/(m3h)
instantaneous rate of propionic acid production
-
h–1
specific growth rate
-
h–1
specific propionic acid production rate
-
D h–1
dilution rate 相似文献
9.
J P Blanc J W Taylor R J Miller E T Kaiser 《The Journal of biological chemistry》1983,258(13):8277-8284
In our approach to beta-endorphin modeling, we have proposed that the biological properties of the natural peptide are determined by the combination of three basic structural units: a highly specific opiate recognition sequence at the NH2 terminus (residues 1-5) connected via a hydrophilic peptide link (residues 6-12) to a potential amphiphilic helix in the COOH-terminal residues 13-31. In the alpha-helical conformation the hydrophobic domain twists around the length of the helix and covers almost one-half of its surface. The other distinctive features of the helix include its basicity and the two aromatic residues Phe18 and Tyr27. In contrast to previous models we have studied, peptide 4 is a "negative" model in the sense that it was designed and examined in order to determine how the lack of a well defined amphiphilic structure affects the biological properties of beta-endorphin. For this purpose, peptide 4 retains the three structural units previously postulated for beta-endorphin, but the amino acids of the 13-31 region are arranged in such a way that no definite continuous hydrophobic zone could be formed in an alpha- or pi-helical conformation of this region. In aqueous buffered solutions, peptide 4 showed almost the same amount of alpha-helical structure as beta-endorphin, with a slight tendency toward less helicity in 50% aqueous 2,2,2-trifluoroethanol. In rat brain homogenate, peptide 4 was degraded slightly slower than beta-endorphin, in contrast to the apparently much higher stability of previous models under the same conditions. With regard to opiate receptor binding, peptide 4 was twice as potent as beta-endorphin in mu-receptor assays but half as potent in delta-receptor assays. The opiate potency of peptide 4 on the guinea pig ileum was higher than that of beta-endorphin. In contrast, in the rat vas deferens assay, which is very specific for beta-endorphin, the potency of peptide 4 was very low and could be shown not to be mediated by the same opiate mechanism or by the same opiate receptor. A comparison of these results with those of previous model peptides provides further evidence for the importance of an amphiphilic helical structure in beta-endorphin residues 13-31, which determines the resistance to proteolysis of the natural molecule and contributes to the delta- and mu-opiate receptor interaction. The amphiphilicity of this helical structure must also be essential for high opiate activity on the rat vas deferens (epsilon-receptors), whereas no such structural requirement appears to be necessary for interaction with the opiate receptors on the guinea pig ileum. 相似文献
10.
Summary The morphological features of intestinal epithelium have been studied by light and electron microscopy in two species; in the rat which is able to absorb proteins, such as antibodies and in the rabbit which does not present any transfer upon oral administration of antibodies.The structure of intestinal absorptive cells of the foetus at term and of the newborn from the first day up to the 20th day of life showed a marked evolution. In the foetal cells the apical quarter of the space between the nucleus and the terminal web presents a well developed smooth endoplasmic reticulum. This reticulum is progressively replaced from the first days of life by large numerous vacuoles which diminish in size and number from the 10th day until they disappear on the 20th day. At that time the cells present the adult picture.This evolution as well as other described structural features of the absorptive cells are similar in the two species, despite functional differences in neonatal protein absorption.
Nous remercions le chef du Centre de Microscopie électronique Monsieur A. Gautier pour ses conseils et ses suggestions intéressantes, Madame M. Probst et Monsieur O. Jenni pour leur aide technique. 相似文献
Nous remercions le chef du Centre de Microscopie électronique Monsieur A. Gautier pour ses conseils et ses suggestions intéressantes, Madame M. Probst et Monsieur O. Jenni pour leur aide technique. 相似文献