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91.
A pharmacological study was undertaken to determine whether the noradrenaline-stimulated breakdown of inositol phospholipids and the potentiation of isoprenaline-stimulated cyclic AMP by noradrenaline in rat cerebral cortex slices are mediated by the same alpha-receptor subtype. The rank order of potency of a range of alpha 1 and alpha 2 antagonists suggests that both responses may involve an alpha 1 receptor, but there were several differences between the pharmacological profiles for the two systems. Although in both cases, all selective alpha 1 antagonists were more potent than alpha 2 antagonists, the rank orders and the absolute potencies differed for the two responses. The inhibition of the inositol phosphate response was characterised by a high alpha 1/alpha 2 antagonist ratio, and in most cases, Hill slopes of inhibition were consistent with the involvement of a single receptor site. Inhibition of the cyclic AMP response had a much lower alpha 1/alpha 2 antagonist ratio and generally exhibited Hill slopes less than one. Evidence has been provided suggesting that adenosine is involved in the potentiation of cyclic AMP and that other, as yet unidentified, factors may also be involved. Even in the absence of an adenosine component, the results presented support the suggestion that the potentiation due to noradrenaline is mediated by a receptor whose identity does not easily fit with the currently accepted classification of alpha adrenoceptors. 相似文献
92.
The possibility that an increased intracellular concentration of cyclic AMP (cAMP) can regulate the extent of muscarinic receptor-stimulated phosphoinositide (PPI) turnover in the human neuroblastoma cell line SK-N-SH was examined. Addition of either forskolin (or its water-soluble analog, L-85,8051), theophylline, isobutylmethylxanthine, or cholera toxin, agents that interact with either the catalytic unit of adenylate cyclase, cAMP phosphodiesterase, or the guanine nucleotide binding protein linked to adenylate cyclase activation, resulted in a 45-181% increase in cAMP concentration and a 27-70% inhibition of carbachol-stimulated inositol phosphate release. Through the use of digitonin-permeabilized cells, the site of inhibition was localized to a step at, or distal to, the guanine nucleotide binding protein that regulates phospholipase C activity. In contrast, when intact SK-N-SH cells were exposed to prostaglandin E1, the ensuing increases in cAMP were not accompanied by an inhibition of stimulated PPI turnover. These differential effects of increased cAMP concentrations on stimulated PPI turnover may reflect the compartmentation of cAMP within SK-N-SH cells. 相似文献
93.
Abstract. The annual cycle of canopy structure in two mediterranean shrubs in a pioneer zone of the mobile dune system in the Donana National Park, Scrophularia frutescens and Halimium halimifolium, has been analyzed. Destructive methods were used as well as a new non-destructive method, based on frequency analysis of organ distribution within the plant canopy. S. frutescens shows strong seasonal changes of photo-synthetic biomass, but little annual increment in dry weight. In H. halimifolium, seasonal changes are not as strongly differentiated as in S. frutescens, but a higher annual increment is shown. The canopy structure of both species and its temporal changes are compared with existingplant strategy models. 相似文献
94.
The calcium-dependent modulation of the affinity of the cyclic nucleotide-gated (CNG) channels for adenosine 3′,5′-cyclic
monophosphate (cAMP) was studied in enzymatically dissociated rat olfactory receptor neurons, by recording macroscopic cAMP-activated
currents from inside-out patches excised from their dendritic knobs. Upon intracellular addition of 0.2 mm Ca2+ (0.2 Ca) the concentration of cAMP required for the activation of half-maximal current (EC50) was reversibly increased from 3 μm to about 30 μm. This Ca2+-induced affinity shift was insensitive to the calmodulin antagonist, mastoparan, was abolished irreversibly by a 2-min exposure
to 3 mm Mg2++ 2 mm EGTA (Mg + EGTA), and was not restored by the application of calmodulin (CAM). Addition of CAM plus 0.2 mm Ca2+ (0.2 Ca + CAM), further reversibly shifted the cAMP affinity from 30 μm to about 200 μm. This affinity shift was not affected by Mg + EGTA exposure, but was reversed by mastoparan. Thus, the former Ca2+-only effect must be mediated by an unknown endogenous factor, distinct from CAM. Removal of this factor also increased the
affinity of the channel for CAM. The affinity shift induced by Ca2+-only was maintained in the presence of the nonhydrolyzable cAMP analogue, 8-bromo-cAMP and the phosphatase inhibitor, microcystin-LR,
ruling out modulation by phosphodiesterases or phosphatases. Our results indicate that the olfactory CNG channels are modulated
by an as yet unidentified factor distinct from CAM.
Received: 26 December 1995/Revised: 14 March 1996 相似文献
95.
Naoyuki Honma Atsuko Uchida Hiroya Hirose Vlastimil Srsen Takeo Kishimoto Shin-ichi Hisanaga 《Journal of neurochemistry》1996,67(5):1856-1865
Abstract: We describe here two types of apoptotic cell death observed in the rat CNS-derived neuroblastoma B50 and B104 cells. One type was induced by dibutyryl cyclic AMP (DBcAMP) after differentiation, and the other was induced by treatment of proliferating cells with cycloheximide. When B50 and B104 cells were treated with 1 m M DBcAMP in the presence of 0.5% fetal calf serum, they began to extend neurites within 12 h and differentiated into neurons at 24 h, as reported previously. However, further cultivation with DBcAMP for up to 72 h led to flotation and, finally, death. Death was by apoptosis as shown by chromatin condensation and DNA fragmentation. Addition of a protein kinase A inhibitor or removal of DBcAMP after differentiation suppressed apoptosis, indicating the involvement of cyclic AMP and protein kinase A in apoptotic cell death. Cell death was also induced in proliferating cells without neurite outgrowth by treatment with cycloheximide. The death was also judged to be by apoptosis based on chromatin condensation and apoptotic body formation, although DNA fragmentation into small sizes was not detected. Both types of cell death showed similar responses to inhibitors for protein kinases and protein phosphatases. 相似文献
96.
Modulation of ζ-Protein Kinase C by Cyclic AMP in PC12 Cells Occurs Through Phosphorylation by Protein Kinase A 总被引:1,自引:1,他引:0
Marie W. Wooten M. Lamar Seibenhener Laura H. Matthews Guisheng Zhou Elaine S. Coleman 《Journal of neurochemistry》1996,67(3):1023-1031
Abstract: Although cyclic AMP (cAMP) has been reported to cross talk with the protein kinase C (PKC) system, effects of elevated intracellular cAMP on the activities of specific PKC isoforms have not been studied. We report findings from a permeabilized cell assay that was used to examine changes in the activity of the atypical PKC isoforms brought about by exposure of PC12 cells to agents that elevate intracellular cAMP. We found that increases in intracellular cAMP led to rapid stimulation of atypical PKC activity, 40–70% above control, for a sustained period of time, a response that occurred independent of the phorbol 12-myristate 13-acetate (PMA)-sensitive PKC isoforms. Changes in intracellular cAMP levels resulted in a dose-dependent redistribution of ζ-PKC to the cytoplasm with a concomitant increase in the phosphorylation state of the enzyme. Incubation of purified ζ-PKC with increasing concentrations of PKA likewise caused a twofold increase in the phosphorylation state of ζ-PKC. In contrast to the positive effect that PKA-mediated phosphorylation had on the activity of ζ-PKC, the enzyme displayed reduced binding to ras when phosphorylated. Taken together, these findings are consistent with the hypothesis that protein phosphorylation of PKC acts as a positive effector of its enzyme activity and may serve as a negative modulator for interaction with other proteins. 相似文献
97.
Ariyuki Kagaya Yosuke Uchitomi Akira Kugaya Minoru Takebayashi Ikuo Nagaoka Mitsutaro Muraoka Norio Yokota Shigeto Yamawaki 《Journal of neurochemistry》1996,66(4):1483-1488
Abstract: We investigated the rapid and slow effects of NaF on intracellular signaling systems such as Ca2+ homeostasis and cyclic GMP (cGMP) generation in rat glioma C6 cells, using the Ca2+ -sensitive dye fura-2 and cGMP enzyme immunoassay. We found that the following: (a) NaF enhanced cGMP generation in a concentration-dependent manner. This enhancement was abolished by pretreatment with 100 µ M BAPTA tetraacetoxymethyl ester or in the presence of W-7 in a concentration-dependent manner. N G -Monomethyl- l -arginine (NMMA), a competitive inhibitor of nitric oxide synthase (NOS), also inhibited the NaF-induced generation of cGMP. These results suggest that NaF-induced cGMP generation occurs via a calcium/calmodulin- and NOS-dependent pathway. (b) The basal intracellular Ca2+ concentration ([Ca2+ ]i ) was transiently greater at 1 and 3 h after pretreatment with NaF. W-7 and W-13 antagonized the increase in [Ca2+ ]i , whereas NMMA had little effect. This suggests that the NaF-induced change in basal [Ca2+ ]i was mediated by a calmodulin-dependent pathway but was independent of a NOS-sensitive pathway. (c) The serotonin (5-HT)-induced intracellular mobilization of Ca2+ was reduced by pretreating the cells with NaF. The reduction in Ca2+ mobilization was antagonized by genistein, a tyrosine kinase inhibitor. W-7, W-5, and H-8 had no effect. Results suggest that NaF differentially regulates the cGMP generation, basal [Ca2+ ]i , and 5-HT2A receptor function in C6 glioma cells. 相似文献
98.
Barbara D. Hettinger-Smith Mark Leid Thomas F. Murray 《Journal of neurochemistry》1996,67(5):1921-1930
Abstract: Chronic treatment with the adenosine receptor antagonist caffeine evokes an up-regulation of A1 adenosine receptors and increased coupling of the receptor to G proteins in rat brain membranes. However, chronic agonist exposure has not been explored. Primary cultures of cerebellar granule cells were exposed chronically to A1 adenosine receptor agonists and antagonists. Exposure to the A1 adenosine receptor agonist N 6 -cyclopentyladenosine resulted in (1) a time- and concentration-dependent reduction in the density of receptors labeled by 1,3-[3 H]dipropyl-8-cyclopentylxanthine, (2) an enhanced ability of guanyl nucleotides to decrease the fraction of A1 adenosine receptor sites displaying high affinity for 2-chloroadenosine, and (3) a functional uncoupling of receptors from adenylyl cyclase (EC 4.6.1.1). The adenosine antagonists caffeine and 8- p -sulfophenyltheophylline produced alterations in A1 adenosine receptor homeostasis that were antipodal to those associated with agonist treatment. Antagonist exposure (1) increased the density of A1 adenosine receptors in cerebellar granule cell membranes, (2) blunted the effect of guanyl nucleotides on receptor coupling to G proteins, and (3) increased the functional coupling of receptors to adenylyl cyclase inhibition. Forskolin treatment of cerebellar granule cells did not affect receptor density, suggesting that cyclic AMP is not involved in the regulation of A1 adenosine receptor expression. 相似文献
99.
Luc De Meester 《Evolution; international journal of organic evolution》1996,50(3):1293-1298
The frequent use of neutral markers to quantify genetic variation in natural populations emphasizes the role of stochastic events in explaining genetic differentiation between populations. Complementary studies on ecologically relevant traits are needed to assess the role of natural selection acting on adaptive variation in the development of local genetic differentiation. To test the hypothesis of local adaptation in the cyclical parthenogenetic species Daphnia magna, the phototactic behavior in the absence and presence of fish kairomone was assayed for 30 clones derived from resting eggs isolated from three habitats characterized by a different predation pressure by fish. Clones derived from populations in which fish are present were, on average, more negatively phototactic in and more responsive to the presence of fish kairomone than clones derived from a fishless habitat. In addition, the results show a high genetic diversity for the traits studied in all three gene pools investigated, indicating a high potential for microevolutionary changes in behavior of these Daphnia populations in the face of changes in predation pressure. The results of the present study indicate that working with large samples at the expense of having less precise estimates of genotypic values for specific genotypes may result in a loss of information with regard to the evolutionary potential of local populations. 相似文献
100.