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1.
Michiko Oka Y. Itoh Shigeru Tatsumi F.-H. Ma Yojiro Ukai Yoshiaki Yoshikuni Kiyoshi Kimura 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(2):189-196
The effect of (+)-5-oxo-D-prolinepiperidinamide monohydrate (NS-105), a novel cognition enhancer, on adenylate cyclase activity
was investigated in cultured neurons of the mouse cerebral cortex. NS-105 (10–7 and 10–6 M) inhibited forskolin-stimulated cyclic AMP formation, an action that was dependent on pertussis toxin-sensitive G proteins.
Conversely, in pertussis toxin-pretreated neurons, NS-105 (10–7 –10–5 M) significantly enhanced the forskolin-stimulated cyclic AMP formation, and this action was completely reversed by cholera
toxin. A metabotropic glutamate receptor agonist (1S, 3R)-1-aminocyclopentane-1, 3-dicarboxylic acid (1S, 3R-ACPD) produced
similar bi-directional actions on the cyclic AMP formation. Both of these inhibitory and facilitatory actions of NS-105 and
1S, 3R-ACPD were blocked by L(+)-2-amino-3-phosphopropinoic acid (L-AP3). NS-105 (10–6 M) and 1S, 3R-ACPD (10–4 M) significantly enhanced isoproterenol- and adenosine-stimulated cyclic AMP formation. The enhancement of such Gs-coupled
receptor agonists-stimulated cyclic AMP formation was also produced by quisqualate but not by L(+)-2-amino-4-phosphonobutanoate
(L-AP4). The phosphoinositides hydrolysis was enhanced by 1S, 3R-ACPD (10–4 M) but not by NS-105 (10–6 M), however, 1S, 3R-ACPD-induced increase in phosphoinositides turnover was attenuated by NS-105. These findings suggest
that NS-105 stimulates metabotropic glutamate receptor subclasses that are coupled both negatively and positively to adenylate
cyclase, but it acts as an antagonist at the receptor subclasses that are linked to phosphoinositides hydrolysis.
Received: 3 February 1997 / Accepted: 25 April 1997 相似文献
2.
Light microscopy of GTP-binding protein (Go) immunoreactivity within the retina of different vertebrates 总被引:2,自引:0,他引:2
Toshio Terashima Toshiaki Katada Eikichi Okada Michio Ui Yoshiro Inoue 《Brain research》1987,436(2):384-389
To examine species differences in the distribution pattern of guanosine triphosphate (GTP)-binding protein (Go) within the vertebrate retina, paraffin-embedded retinae from a number of vertebrate species, including the goldfish, frog, turtle, chicken, monkey, and human, were immunohistochemically stained with affinity-purified antibody against the alpha-subunit of Go. Go-immunoreactive products were found to be located in the neuropil, but not in the cell bodies of neurons, in the retina of all these species. However, some species differences were observed. In the frog, monkey and human, the inner plexiform layer (IPL) was homogeneously stained with this antibody, but in the goldfish, turtle and chicken, the IPL was heterogeneously stained. In the frog, chicken, turtle and human, the outer plexiform layer (OPL) was densely stained with this antibody, but in the goldfish and monkey, the OPL was rather faintly immunoreactive to the antibody. In the goldfish, monkey and human, the outer nuclear layer (ONL) was not immunoreactive to the Go-antibody, whereas in the frog, turtle and chicken, the ONL was immunoreactive to it. The implications of these species differences in Go localization in the vertebrate retina are discussed. 相似文献
3.
F. Okada T. J. Crow G. W. Roberts 《Journal of neural transmission (Vienna, Austria : 1996)》1991,84(1-2):147-153
Summary We have measured the amount of Gi (the inhibitory G-protein) or Go (a similar G-protein of unknown function) in 5 areas of the medial temporal lobe of control and schizophrenic brains utilizing pertussis toxin-catalyzed ADP ribosylation. The material used has previously been shown to have asymmetrical structural abnormalities of the ventricular system. The amount of Gi or Go was reduced on the left side in the hippocampus, amygdala and parahippocampal gyrus, the difference reaching significance in the hippocampus. This data is the first report of a neurochemical correlate of the structural change in the brains of patients with schizophrenia. Decreased Gi or Go in hippocampus may relate to other reported neurochemical deficits or other transmembrane signalling abnormalities. Further investigations of these indices of secondary messenger function in relation to structural changes are indicated. 相似文献
4.
Dr. A. Härfstrand K. Fuxe L. Agnati B. Fredholm 《Journal of neural transmission (Vienna, Austria : 1996)》1989,75(2):83-99
Summary Interactions between a 2-adrenoreceptor agonist and neuropeptide Y (NPY) binding sites have been studied in the rat medulla oblongata (MO) using biochemical binding techniques as well as quantitative autoradiography. Tritiated para-amino clonidine (3H-PAC; 2-adrenoceptor agonist), idazoxan (3H-IDA; 2-adrenoceptor antagonist) and iodinated neuropeptide Y (125I-NPY) were used as radioligands. (1) Neuropeptide Y (NPY; 10–8M) but not bovine pancreatic polypeptide (BPP) nor peptide YY (PYY 10nM) increased the KD value of3H-PAC binding sites. However, intraventricular administration of a high dose of NPY (1.25nmol) did not change the3H-PAC binding characteristics in MO membrane preparations of these animals. (2) GTP 10–4 lowered the affinity of3H-PAC binding. NPY (10 nM) had no additional effect, nor did NPYinfluence the GTP induced shift in potency of clonidine to displace3H-IDA from its binding sites. (3) In the autoradiographical experiments NPY (10nM) significantly reduced3H-PAC binding (2nM) in the nucleus tractus solitarius (NTS) area by 35%. (4) When clonidine, either given centrally in vivo (3.75nmol) or in vitro (10 nM) the binding of125I-NPY was reduced (34 and 24%, respectively) in the NTS. When the monoamine receptors were irreversibly blocked in vivo by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 10 g i.e. 24h)125I-NPY (0.5 nM) binding was increased by 137% in the NTS. This effect of EEDQ was prevented by pretreatment with the 2-adrenoreceptor antagonist idazoxan.These results provide support for a direct intramembrane interaction between the 2-receptor and the NPY receptor within the NTS and may be of importance in central cardiovascular regulation. 相似文献
5.
Joanna S. Kruszewska Markku Saloheimo Merja Penttilä Grażyna Palamarczyk 《Current genetics》1998,33(6):445-450
A cDNA coding for GTP: α-d-mannose-1-phosphate guanyltransferase (MPG1 transferase) (EC 2.7.7.13) was isolated from a cDNA library of the Trichoderma reesei RutC-30 strain by suppression of the yeast Saccharomyces cerevisiae mutation in the DPM1gene encoding mannosylphosphodolichol (MPD) synthase. The nucleotide sequence of the 1.6 kb-long cDNA revealed an ORF which
encodes a protein of 364 amino acids. Sequence comparisons demonstrate 70% identity with the S. cerevisiae guanyl transferase gene (MPG1) and 75% identity with the Schizosaccharomyces pombe homologue. No similarity was found with the MPD synthase encoded by the S. cerevisiae DPM1 gene. The possibility that cloned cDNA encodes a product with a MPD synthase activity was also excluded by transforming a
heterozygous S. cerevisiae dpm1::LEU2/DPM1 diploid, which did not lead to the restoration of viability of the dpm1 spores. Simultaneously, a significant increase in MPG transferase activity, as compared with the wild-type yeast, was observed
in cellular extracts when the mpg1 cDNA from Trichoderma was expressed in the S. cerevisiae dpm1-6 mutant.
Received: 21 July 1997 / 24 April 1998 相似文献
6.
The effect of both intrahypothalamic and systemic administration of guanosine triphosphate (GTP) on lordosis behavior was studied in ovariectomized and ovariectomized-adrenalectomized, estrogen-primed rats (estradiol benzoate, 4 μg). This estrogen dose per se induced only weak or no lordosis behavior. Injection of GTP into the medial hypothalamic area (100 μg in 2.5 μl) elicited lordosis behavior with relatively short latency in 6 out of 7 rats. Systemic administration of GTP in a dose range of 0.8 mg to 5.0 mg to ovariectomized estrogen-primed rats, stimulated intense lordosis behavior in all subjects. Weak lordosis responses were displayed within the first 12 hr after GTP injection, but at 48 hr all rats were highly estrous. Lordosis behavior remained for up to eight days, its duration being related to the dose of GTP administered. GTP (2 mg) induced lordosis behavior in ovariectomized, adrenalectomized estrogen-primed rats, thus excluding the participation of adrenal steroids in this effect. The results are interpreted in terms of the stimulation of adenyl cyclase-cAMP systems by GTP. 相似文献
7.
8.
Susanne Ott Tommaso Costa Albert Herz 《Naunyn-Schmiedeberg's archives of pharmacology》1986,334(4):444-451
Summary Equilibrium binding isotherms of [3H]diprenorphine in membranes from NG 108-15 cells are consistent with a homogenous population of binding sites. Upon addition of Na+, Mg2+ and GTP, only a 2-fold reduction in affinity with a minor decrease in the number of sites is observed. Dissociation curves of [3H]diprenorphine, however, are clearly biphasic: in the absence of Na+, Mg2+ and GTP, 80% of the bound ligand dissociates slowly with at
1/2 of 100 min, and only 20% rapidly (t
1/2 4.5 min). In the presence of Mg2+, nearly all the binding is found in the slowly dissociating form. Upon the addition of either Na+ or GTP, 20–30% of the binding dissociates more rapidly. The rate constant of the rapidly dissociating form generated by Na+, however, is 2.5 times greater than that induced by the presence of GTP. Thus, the addition of both, Na+ and GTP, converts about 80% of the receptor into a very fast dissociating form (t
1/2 1.7 min).Exposure of intact cells to pertussis toxin (10 ng/ml) or treatment of membranes with N-ethyl maleimide (500 M), strongly reduces the proportion of the slowly dissociating component. Following these treatments, the effect of GTP is reduced or abolished, but that of Na+ remains unaffected.We conclude from these data that the effects of Na+ and GTP are not only distinct in site but also in mechanism of action and that there are three forms of opioid receptors that can be differentiated by their kinetic properties. The slowly dissociating receptor form requires a functional N unit. 相似文献
9.
The lactogen receptor has been suggested to associate with one or more G proteins despite the absence of a 7-transmembrane
spanning sequence. These studies were designed to determine whether lactogens acutely increase GTP binding to or GTPase activity
in Nb2 cell membrane. Incubation of Nb2 cell membrane with either ovine PRL (10 ng/ml) or diluent for 0–1 h resulted in a
decrease in total35S-GTP binding to both with no difference in GTP binding between PRL- and diluent-treated membranes. There was also no change
in35S-GTP binding to Nb2 cell membrane incubated with increasing oPRL concentrations (0.001–100 ng/ml) for 60 min. α-32P-GTP photoaffinity labelling was used to evaluate changes in GTP binding to specific G proteins. Photoaffinity labelling
of α-32P-GTP to no G protein was changed after preincubation with oPRL (10 ng/ml) for 0–60 min or with oPRL (0.01–10 ng/ml) for 60
min. Finally, it was determined whether oPRL had any acute effect on GTPase activity, as determined by release of32Pi from γ-32P-GTP. When Nb2 cell membrane was preincubated for 0–60 min with oPRL (10 ng/ml) or a range of oPRL concentrations (0–10 ng/ml),
no change in GTPase activity was observed. However, when Nb2 cells were incubated with lactogen for 0–7 h, GTPase activity
in equal quantities of Nb2 cell membrane prepared from those cells increased over time. Increased GTPase activity (64.9–74.4%;P<0.03 compared to 0 h) was observed after 4–7 h incubation with lactogen.
In summary, addition of lactogen to Nb2 cell membrane did not acutely increase either GTP binding or GTPase activity. Yet
when Nb2 cells were incubated with lactogen for 4 h prior to preparation of membrane, GTPase activity was significantly increased.
This evidence, in addition to our previous results showing that 4 h incubation with lactogen increased G protein β subunit
concentration and pertussis toxin-stimulated ADP-ribosylation of Gi, support a role for delayed lactogen modulation of one
or more G proteins in the Nb2 cell, requiring at least 4 h for maximal effect. 相似文献
10.
M. Schwanstecher S. Löser I. Rietze U. Panten 《Naunyn-Schmiedeberg's archives of pharmacology》1991,343(1):83-89
Summary In microsomes obtained from mouse pancreatic islets, the Mg complex of adenosine 5-triphosphate (MgATP) increased the dissociation constant (K
D) for binding of [3H]glibenclamide by sixfold. In the presence of Mg2+, not only ATP but also adenosine 5-0-(3-thiotriphosphate) (ATPS), adenosine 5-diphosphate (ADP), guanosine 5-triphosphate (GTP), guanosine 5-diphosphate (GDP), guanosine 5-0-(3-thiotriphosphate) (GTPTS) and guanosine 5-0-(2-thiodiphosphate) (GDP S) inhibited binding of [3H]glibenclamide. These effects were not observed in the absence of Mg2+. Half maximally effective concentrations of the Mg complexes of ATP, ADP, ATPS and GDP were 11.6, 19.0, 62.3 and 90.1 mol/l, respectively. The non-hydrolyzable analogues adenosine 5-(,-imidotriphosphate) (AMP-PNP) and guanosine 5-(,-imidotriphosphate) (GMP-PNP) did not alter [3H]glibenclamide binding in the presence of Mg2+. MgADP acted much more slowly than MgATP and both MgADP and MgADP did not inhibit [3H]glibenclamide binding when the concentrations of MgATP and MgATP were kept low by the hexokinase reaction. Development of MgATP-induced inhibition of [3H]glibenclamide binding and dissociation of [3H]-glibenclamide binding occurred at similar rates. However, the reversal of MgATP-induced inhibition of [3H]glibenclamide binding was slower than the association of [3H]glibenclamide with its binding site. Exogenous alkaline phosphatase accelerated the reversal of MgATP-induced inhibition of [3H]glibenclamide binding. MgATP enhanced displacement of [3H]glibenclamide binding by diazoxide. The data suggest that sulfonylureas and diazoxide exert their effects by interaction with the same binding site at the sulfonylurea receptor and that protein phosphorylation modulates the affinity of the receptor.Some of the results described here are part of the medical theses of S. Löser and I. Rietze
Send offprint requests to M. Schwanstecher at the above address 相似文献