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91.
Reconstitution of somatostatin and muscarinic receptor mediated stimulation of K+ channels by isolated GK protein in clonal rat anterior pituitary cell membranes 总被引:10,自引:0,他引:10
A Yatani J Codina R D Sekura L Birnbaumer A M Brown 《Molecular endocrinology (Baltimore, Md.)》1987,1(4):283-289
Somatostatin (SS) inhibits secretion from many cells, including clonal GH3 pituitary cells, by a complex mechanism that involves a pertussis toxin (PTX)-sensitive step and is not limited to its cAMP lowering effect, since secretion induced by cAMP analogs and K+ depolarization are also inhibited. SS also causes membrane hyperpolarization which may lead to decreases in intracellular Ca2+ need for secretion. Using patch clamp techniques we now demonstrate: 1) that both (SS) and acetylcholine applied through the patch pipette to the extracellular face of a patch activate a 55-picosiemens K+ channel without using a soluble second messenger; 2) that, after patch excision, the active state of the ligand-stimulated channel is dependent on GTP in the bath, is abolished by treatment of the cytoplasmic face of the patch with activated PTX and NAD+, and after inactivation by PTX, is restored in a GTP-dependent manner by addition of a nonactivated human erythrocyte PTX-sensitive G protein, and 3) that the 55-picosiemens K+ channel can also be activated in a ligand-independent manner with guanosine [gamma-thio] triphosphate (GTP gamma S) or with Mg2+/GTP gamma S-activated erythrocyte G protein. We call this protein GK. It is an alpha-beta-gamma trimer of which we have previously shown that the alpha-subunit is the substrate for PTX and that it dissociates on activation with Mg2+/GTP gamma S into alpha-GTP gamma S plus beta-gamma. A similarly activated and dissociated preparation of GS, the stimulatory regulatory component of adenylyl cyclase, having a different alpha-subunit but the same beta-gamma-dimer, was unable to cause K+ opening.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
92.
Mammalian DNA polymerase alpha: a replication-competent holoenzyme form from calf thymus 总被引:1,自引:0,他引:1
U Hübscher M Gassmann S Spadari N C Brown E Ferrari H J Buhk 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》1987,317(1187):421-428
Calf thymus DNA polymerase alpha, like the replication-specific DNA polymerase III holoenzyme of Escherichia coli, can be isolated as a distinct complex. A specific multiprotein form of the polymerase alpha, a form designated replication-competent (RC) holoenzyme, consists of a complex of a polymerase-primase core and at least six other polypeptides. The RC holoenzyme can efficiently replicate several naturally occurring templates, including the genomic DNA of the porcine circovirus (PCV). The DNA of this virion consists of a single-stranded circle with a defined replication origin, and its replication requires the cellular DNA replication machinery. It might therefore provide an invaluable opportunity to investigate chromosomal replication mechanisms, analogous to the way that studies on E. coli bacteriophage DNA replication elucidated host DNA replication mechanisms. Calf RC holoenzyme alpha selectively initiates PCV DNA replication in vitro at a site that possibly represents a consensus sequence of cellular DNA replication origins. The cell-free PCV replication system will be exploited for the in vitro dissection and reconstitution of the RC holoenzyme and the functional analysis of its component polypeptides. 相似文献
93.
Light induces a rapid and transient increase in inositol-trisphosphate in toad rod outer segments 总被引:1,自引:0,他引:1
J E Brown C Blazynski A I Cohen 《Biochemical and biophysical research communications》1987,146(3):1392-1396
The sub-second time course of changes in the content of [3H]inositol-1,4,5-trisphosphate was determined in rod outer segments from very rapidly frozen Bufo retinas that had been incubated with [3H]inositol. Rod outer segments were cut off frozen specimens with a cryostat microtome and the water soluble extracts were analyzed. The content of [3H]inositol-1,4,5-trisphosphate rose after approximately 250 msec of bright illumination, but returned to the unstimulated level after 1 sec, whether the stimulus remained on or not. That is, there was rapid but transient change in the content of [3H]inositol-1,4,5-trisphosphate after the onset of stimulation. 相似文献
94.
95.
M J Engle M Dooley D J Brown 《Biochemical and biophysical research communications》1987,145(1):397-401
Fetal rabbit lungs from 23 day gestation animals were used to investigate the potential role of lactate as a substrate for fetal lung glycogen synthesis. Fetal lactate dehydrogenase activity was approximately twice that found in the adult lung, while the activity of phosphoenolpyruvate carboxykinase was elevated fourfold over the adult value. Pyruvate carboxylase activities were similar in both fetal and adult lungs. Studies employing fetal lung explants in organ culture indicated that the presence of both glucose and lactate may be necessary for glycogen accumulation in the developing fetal lung. These data support the hypothesis that lactate is an important precursor for fetal lung glycogen. 相似文献
96.
Recently, work in this laboratory has shown that changes in the 'dynamic' component of fluidity, lipid composition and phospholipid methylation activity of distal colonic brush-border membranes could be detected after administration of 1,2-dimethylhydrazine to rats of the Sherman strain for 5-15 weeks, i.e., before the development of colon cancer. The present experiments were therefore conducted to: determine whether similar 'premalignant' biochemical changes could be detected in basolateral membranes of Sherman rats treated with this agent; and clarify the relationship of these membrane changes to the malignant transformation process by examining the effect of 1,2-dimethylhydrazine on these biochemical parameters in colonic antipodal plasma membranes of rats of the Lobund-Wistar strain. This particular strain of rats has previously been shown to be total resistant to the induction of tumors by 1,2-dimethylhydrazine. The results of the present experiments demonstrate that similar biochemical alterations could not be detected in the colonic plasma membranes prepared from either strain of rat treated with 1,2-dimethylhydrazine. These data support the contention that the prior biochemical membrane alterations noted in brush-border membranes of 1,2-dimethylhydrazine-treated animals are, in fact, related to the malignant transformation process and, furthermore, are confined to the luminal surface of distal colonic epithelial cells. 相似文献
97.
To determine the mode of action of the beta-glucosidase from Trichoderma reesei a method was developed for synthesizing [1-3H]cello-oligosaccharides with specific radioactivities of approximately 3000 Ci/mol. The beta-glucosidase removed glucosyl residues from the non-reducing end of the [1-3H]cello-oligosaccharides in a multiple attack mode with little tendency to attack the substrates repetitively. Values of Km were lower for longer cello-oligosaccharides, whereas values of V remained essentially constant. A subsite map, constructed using values of V/Km for the cello-oligosaccharides, showed that the substrate-binding region comprises primarily three subsites. 相似文献
98.
Wind chill is defined as the excess of sensible heat loss over what would occur at zero wind speed with other conditions unchanged. Wind chill can be broken down into a part that is determined by air temperature and a radiative part that comprises wind-dependent effects on additional long-wave radiative exchange and on solar radiation (by reducing solar warming). Radiative exchange and gain from solar radiation are affected by changes that are produced by wind in both surface and fleece insulations. Coefficients are derived for (a) converting the components of sensible heat exchange (air-temperature-dependent including both convective and associated long-wave radiative, additional long-wave radiative and solar) into the components of the total heat loss that are associated with wind and (b) for calculating equivalent air temperature changes. The coefficients contain terms only in wind speed, wetting of the fleece and fleece depth; these determine the external insulation.Calculation from standard meteorological records, using Plymouth and Aberdeen in 1973 as examples, indicate that in April–September 1973 at Plymouth reduction in effective solar warming constituted 28% of the 24-h total wind chill, and 7% in the other months of the year combined; at Aberdeen the corresponding percentages were 25% and 6%. Mean hour-of-day estimates for the months of April and October showed that at midday reduction in solar warming due to wind rose to the order of half the air-temperature-dependent component of wind chill, with a much smaller effect in January. For about six hours at midday in July reduction in solar warming due to wind was similar in magnitude to the air-temperature-dependent component.It is concluded that realistic estimates of wind chill cannot be obtained unless the effect of solar radiation is taken into account. Failure to include solar radiation results not only in omitting solar warming but also in omitting the effects of wind in reducing that warming.The exchange of sensible (non-evaporative) heat loss between a homeothermic animal and its environment can be divided into two parts: one part is due to the temperature difference between the animal and the surrounding air, and the other part is due to additional long-wave radiative exchange between animal and environment and to solar radiation. Both parts of the heat exchange are determined in magnitude by the animal's thermal insulation, which is itself affected by windspeed and wetting. Wind diminishes as animal's external insulation, so increasing heat loss under all conditions when the air temperature is lower than the animal's surface temperature: this effect is termed wind chill. Wind chill has previously been investigated more commonly in relation to man (Burton an Edholm, 1955; Smithson and Baldwin, 1978; Mumford, 1979; Baldwin and Smithson, 1979). This paper is concerned with the separate contributions to wind chill calculated for sheep that can be associated with convective and radiative heat exchanges. 相似文献
99.
B M Foxwell D C Blakey A N Brown T A Donovan P E Thorpe 《Biochimica et biophysica acta》1987,923(1):59-65
Deglycosylation of ricin may be necessary to prevent the entrapment of antibody-ricin conjugates in vivo by cells of the reticuloendothelial system which have receptors that recognise the oligosaccharide side chains on the A- and B-chains of the toxin. Carbohydrate-deficient ricin was therefore prepared by recombining the A-chain, which had been treated with alpha-mannosidase, with the B-chain, which had been treated with endoglycosidase H or alpha-mannosidase or both. By recombining treated and untreated chains, a series of ricin preparations was made having different carbohydrate moieties. The removal of carbohydrate from the B-chain did not affect the ability of the toxin to agglutinate erythrocytes, and alpha-mannosidase treatment of the A-chain did not affect its ability to inactivate ribosomes. The toxicity of ricin to cells in culture was only reduced in those preparations containing B-chain that had been treated with alpha-mannosidase, when a 75% decrease in toxicity was observed. The toxicity of the combined ricin preparation to mice varied from double to half that of native ricin, depending on the chain(s) treated and the enzymes used. Removal of carbohydrate greatly reduced the hepatic clearance of the toxin and the levels of toxin in the blood were correspondingly higher. These results suggest that antibody-ricin conjugates prepared from deglycosylated ricin would be cleared more slowly by the liver, inflict less liver damage, and have greater opportunity to reach their target. 相似文献
100.
Protein kinase C-mediated negative-feedback inhibition of unstimulated and bombesin-stimulated polyphosphoinositide hydrolysis in Swiss-mouse 3T3 cells. 总被引:16,自引:9,他引:7
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Bombesin-related peptides stimulate a rapid increase in polyphosphoinositide hydrolysis in Swiss-mouse 3T3 cells. These peptides generate an increase in the efflux of 45Ca2+ from pre-labelled cells, a response consistent with an inositol trisphosphate-mediated mobilization of intracellular Ca2+. The bombesin-stimulated release of cellular 45Ca2+ is inhibited by tumour-promoting phorbol esters (e.g. 12-O-tetradecanoylphorbol 13-acetate, TPA). Although there are several possible sites of action at which this effect might occur, our results indicate that TPA induces an uncoupling of bombesin-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) without decreasing cellular binding of bombesin. In cultured cells, protein kinase C can be down-modulated by a prolonged incubation of the cells with phorbol esters. Such pretreatment greatly decreased the inhibitory effect of TPA on bombesin-stimulated PIP2 hydrolysis, suggesting that this action of the phorbol ester is mediated via protein kinase C. Since diacylglycerol is an endogenous activator of protein kinase C and a direct product of PIP2 hydrolysis, these results suggest that protein kinase C inhibition of polyphosphoinositide hydrolysis may function as a negative-feedback pathway. Cells in which protein kinase C has been down-modulated show elevated basal and bombesin-stimulated production of inositol phosphates, providing evidence that such a feedback loop limits polyphosphoinositide turnover in both unstimulated and mitogen-stimulated cells. 相似文献