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1.
Stimulation of P2-purinergic receptors by ATP resulted in activation of phosphorylase, which was associated with marked production of inositol trisphosphate (Ins-P3), in rat hepatocytes. ATP also inhibited forskolin-induced accumulation of cAMP in the presence of a phosphodiesterase inhibitor. On the contrary, adenosine or AMP never inhibited the cAMP accumulation, but increased hepatocyte cAMP; the stimulation was antagonized by a methylxanthine. Thus, P1-purinergic receptors are linked to adenylate cyclase in a stimulatory fashion in hepatocytes. Various kinds of purine nucleotides stimulating P2-receptors can be divided into two groups on the basis of their relative abilities to stimulate Ins-P3 production and to inhibit cAMP accumulation; the first group including adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), ADP, 5-adenylyl imidodiphosphate, GTP, and guanosine 5'-O-(3-thiotriphosphate) has an efficacy similar to that of ATP, and the second group of nucleotides including alpha, beta-methyleneadenosine 5'-triphosphate, beta, gamma-methyleneadenosine 5'-triphosphate (App(CH)2)p), and GDP exerts considerable inhibitory effects on cAMP accumulation, but only slight effects on inositol lipid metabolism. Treatment of hepatocytes with islet-activating protein, pertussis toxin, blocked the nucleotide-induced inhibition of cAMP accumulation, but exerted only a small effect on Ins-P3 production. In membranes prepared from hepatocytes, forskolin-stimulated adenylate cyclase was inhibited by GTP. This GTP-induced inhibition of the enzyme was susceptible to islet-activating protein and dependent on the concentration of ATP (or its derivatives, ATP gamma S or App(CH2)p). It is concluded that there are two types of P2-purinergic receptors: one is linked to adenylate cyclase via an inhibitory guanine nucleotide regulatory protein (Gi) and the other is linked to phospholipase C. 相似文献
2.
Purification of GTP-binding proteins from bovine brain membranes. Identification of heterogeneity of the alpha-subunit of Go proteins 总被引:3,自引:0,他引:3
Using high-resolution Mono Q column chromatography, we purified 6 distinct peaks of GTP-binding proteins from bovine brain membranes. Five of them consisted of 3 polypeptides with alpha beta gamma-subunits and served as the substrate of islet-activating protein (IAP), pertussis toxin. The other one was purified as alpha-subunit alone and was also ADP-ribosylated by IAP in the presence of beta gamma-subunits. When each alpha-subunit was characterized by immunoblot analysis using various antibodies with defined specificity, the two of them were identified as Gi-1 and Gi-2, and other 4 appeared to be Go or Go-like G proteins. The alpha-subunits of immunologically Go-like proteins were apparently distinguishable from one another on elution profiles from the Mono Q column. Thus, there was a heterogeneity of the alpha-subunit of Go in the brain membranes. 相似文献
3.
Y Fujinaga N Morozumi K Sato Y Tokumitsu K Fujinaga Y Kondo M Ui F Okajima 《FEBS letters》1989,245(1-2):117-121
Acute spontaneous c-myc gene expression and sustained increase of a GTP-binding protein(s) (G-protein) which is sensitive to islet-activating protein (IAP), pertussis toxin, occurred early during primary culture of adult rat hepatocytes. Following these earlier events, DNA synthesis was demonstrated in response to EGF and insulin. Addition of IAP immediately after plating of primary cultures inhibited c-myc expression and the hormone-induced DNA synthesis. Addition at 24 h or later following cell inoculation, however, produced only weak effects on DNA synthesis, even though the IAP-sensitive G-proteins were completely inactivated. We conclude that the IAP-sensitive G-protein(s) plays a role in the earlier process(es) of the G0-G1 transition, which is essential for the initiation of growth factor-dependent DNA synthesis. 相似文献
4.
Norio Ogawa Kiminao Mizukawa Kumiko Haba Masato Asanuma Akitane Mori 《Neurochemical research》1992,17(7):687-691
We assayed N-methyl-d-aspartate (NMDA) receptors [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP) bindings) and evaluated their distribution in the brain by quantitative autoradiography in young adult and aged rats. In the young adult rats, NMDA receptors were present at relatively high concentrations in the cerebral cortex and hippocampus. In the aged rats, NMDA receptors were decreased in the nealy all areas of the brain, especially in the cerebral cortex and hippocampus. Chronic administration of bifemelane hydrochloride, a drug for sequela of cerebrovascular diseased, at a dose of 15 mg/kg/day for 14 days, markedly attenuated these decrease in NMDA receptors. Since NMDA receptors are considered to be involved in memory and learning processes, our results suggest that bifemelane hydrochloride may be applicable to the treatment of disturbed memory and learning. 相似文献
5.
6.
A chemotactic peptide stimulated the high-affinity GTPase activity in membrane preparations from guinea pig neutrophils. The enzyme stimulation was inhibited by prior exposure of the membrane-donor cells to islet-activating protein (IAP), pertussis toxin, or by direct incubation of the membrane preparations with its A-protomer (the active peptide) in the presence of NAD. The affinity for the chemotactic peptide binding to its receptors was lowered by guanyl-5'-yl beta, gamma-imidodiphosphate (Gpp(NH)p) reflecting its coupling to the guanine nucleotide regulatory protein in neutrophils. The affinity in the absence of Gpp(NH)p was lower, but the affinity in its presence was not, in the A-protomer-treated membranes than in nontreated membranes. The inhibitory guanine nucleotide regulatory protein of adenylate cyclase (Ni) was purified from rat brain, and reconstituted into the membranes from IAP-treated cells. The reconstitution was very effective in increasing formyl-Met-Leu-Phe-dependent GTPase activity and increasing the chemotactic peptide binding to membranes due to affinity increase. The half-maximal concentration of IAP to inhibit GTPase activity was comparable to that of the toxin to inhibit the cellular arachidonate-releasing response which was well correlated with ADP-ribosylation of a membrane Mr = 41,000 protein (Okajima, F., and Ui, M. (1984) J. Biol. Chem. 259, 13863-13871). It is proposed that the IAP substrate, Ni, couples to the chemotactic peptide receptor and mediates arachidonate-releasing responses in neutrophils, as it mediates adenylate cyclase inhibition in many other cell types. 相似文献
7.
Summary New cell lines, designated as ML-DmDl≈10, were established from dissociated imaginal discs ofDrosophila melanogaster. The culture medium was prepared by mixing in a 1:1 ratio Cross and Sang’s M3(BF) medium, supplemented with 10% heat inactivated
fetal bovine serum (FBS), with the supernatant of a primary embryonic cell culture made in the M3(BF) medium and supplementing
this mixture with insulin. One cell line was established in the medium containing larval hemolymph instead of the primary
culture supernatan, and another was established in fresh M3(BF) medium supplemented with insulin and FBS. In these mediums,
imaginal disc cells first formed aggregates and cellular vesicles within a few weeks followed by the proliferation of thin-layered
cells around them after about 1 mo. Ten cell lines have so far been established from two kinds of imaginal discs and disc
mixtures. The ploidy of these cell lines was predominantly diploid. Population doubling time was about 50 to 70 h at 3 to
10 mo. after initiation of the culture. When the cell aggregates formed in vitro were implanted in metamorphosing larvae,
they differentiated at high frequency into adult cuticular strutures in the early phase of the primary culture. This differentiation
of aggregates was also observed, though at low frequency, in a culture maintained by dilution-transfer for 6 to 15 mo. in
vitro. 相似文献
8.
A role of the B-oligomer moiety of islet-activating protein, pertussis toxin, in development of the biological effects on intact cells 总被引:52,自引:0,他引:52
Islet-activating protein (IAP), pertussis toxin, is an oligomeric protein (Tamura, M., Nogimori, K., Murai, S., Yajima, M., Ito, K., Katada, T., Ui, M., and Ishii, S. (1982) Biochemistry 21, 5516-5522), the biggest subunit (Mr = 28,000, referred to as the A-protomer) of which catalyzes transfer of the ADP-ribose moiety of NAD to the membrane Mr = 41,000 protein. The pentamer, termed the B-oligomer, consisting of the residual subunits was the moiety of IAP that was responsible for binding to the cell surface, as revealed by competitive inhibition of the development of the IAP actions on intact rat C6 glioma cells and rat adipocytes. The binding of the B-oligomer to its receptor proteins was divalent via the constituent two dimers; it stimulated mitosis of lymphocytes and caused an insulin-like action to enhance glucose oxidation in adipocytes, just as did concanavalin A, presumably as a result of cross-linking or aggregation of the membrane proteins. The A-promoter displayed its biological action on adipocytes only when the B-oligomer had been bound to the cells. Thus, IAP is a typical A-B toxin in which the B-oligomer is first bound to the cell surface proteins to enable the A-protomer to reach to the site of its action within the cell. Diverse biological actions of pertussis toxin may be accounted for by the mitogenic action of the B-oligomer as well as ADP-ribosyltransferase activity of the A-promoter. 相似文献
9.
10.
Midori Hiramatsu Kumiko Haba Rei Edamatsu Hajime Hamada Akitane Mori 《Neurochemical research》1989,14(3):249-251
The effect of a Chinese herbal medicine Sho-saiko-to-go-keishi-ka-shakuyaku-to (TJ-960) on the brain choline acetyltransferase (CAT) activity was studied in adult (3.5 months of age) and aged (24 months of age) rats. After oral administration of 5% TJ-960 solution for 3 months, CAT activity in the hippocampus, pons-medulla oblongata and striatum of aged rats was significantly lower than that of adult rats. CAT activity in the cerebellum, however, was significantly higher in the aged rats, as compared to the adult rats. TJ-960 significantly increased CAT activity in the hippocampus and striatum of aged rats, but did not affect the activity of the enzyme in the adult rat brain. 相似文献