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1.
The beta-adrenergic agonist 1-isoproterenol induced an early (less than 1 min) stimulation of endocytosis, amino acid transport and hexose transport, monitored by the temperature-sensitive uptake of horseradish peroxidase, alpha-aminoisobutyrate and 2-deoxyglucose, respectively, in rat ventricle cubes. This stimulation was time- and concentration-dependent and was maximum at 10(-8) M isoproterenol. The beta-adrenergic antagonist propranolol blocked isoproterenol stimulation of membrane transport, thereby confirming beta-adrenoceptor mediation; 2.5 mM EGTA, 1 mM LaCl2 and 100 microM verapamil blocked the hormonal response without affecting basal transport. The calcium ionophore A23187 caused an acute stimulation of endocytosis, hexose and amino acid transport. Isoproterenol rapidly (less than 30 s) stimulated 45Ca2+ influx. These data suggest that stimulus-response (stimulus-"transport") coupling is mediated by a rise in cytosolic Ca2+ concentration. A rapid (less than 30 to 60 s) increase in ornithine decarboxylase (ODC) activity, followed by an early (less than 1 to 2 min), sustained increase in putrescine, spermidine and spermine concentrations was evoked by 10(-7) M isoproterenol. The ODC inhibitor alpha-difluoromethylornithine (DFMO, 5 mM) suppressed the isoproterenol-induced increase in ODC and polyamine levels and the stimulation of 45Ca influx, endocytosis, hexose transport, and amino acid transport. Putrescine (0.5 mM) negated DFMO inhibition and restored the increase in polyamines, 45Ca influx, endocytosis, and transport of hexose and amino acid. These data suggest that polyamine synthesis is involved in isoproterenol stimulation of Ca2+ influx and membrane transport functions in ventricular myocardium. These findings are consistent with a model for signal transduction and stimulus-response coupling in which polyamines function as intracellular messengers to generate cytosolic Ca2+ signals by stimulating Ca2+ influx.  相似文献   

2.
The androgenic steroid hormone testosterone induced an early (less than 30-60 seconds) stimulation of endocytosis, hexose transport, and amino acid transport, monitored by the temperature-sensitive uptake of horseradish peroxidase, 2-deoxyglucose, and alpha-aminoisobutyrate, respectively, in rat ventricle cubes and acutely isolated ventricular myocytes. This stimulation was time- and concentration-dependent and was maximal at 10(-9) to 10(-8) M testosterone, consistent with androgen-receptor mediation. EGTA (2.5 mM), La3+ (1 mM), and verapamil (100 microM) ablated the hormonal response. The calcium ionophore A23187 (10 microM) induced an acute stimulation of endocytosis, amino acid transport, and hexose transport which was not further increased by testosterone (10(-8) M), suggesting a common effector pathway. Testosterone (10(-8) M) also evoked a rapid (less than 30 seconds) stimulation of 45Ca influx and efflux. Testosterone (10(-8) M) induced a rapid (less than 5 seconds) transient increase in ornithine decarboxylase (ODC) activity peaking (twofold to threefold) at 60 seconds, and an early (15 seconds) transient accumulation of polyamines peaking at 60 seconds in isolated myocytes. The specific, irreversible ODC inhibitor alpha-difluoromethylornithine (DFMO, 5-10 mM) blocked the testosterone-evoked increase in ODC activity and polyamine levels and the stimulation of Ca2+ fluxes, endocytosis, hexose transport, and amino acid transport. Putrescine (0.5-1 mM), the ODC product, reversed DFMO inhibition and restored the increase in polyamines, 45Ca fluxes, and Ca2+-dependent membrane transport processes. These results demonstrate that rapid, transient ODC-regulated polyamine synthesis is essential for androgenic stimulation of Ca2+ fluxes and membrane transport processes in ventricular myocytes. These findings support a model for signal transduction in which newly synthesized polyamines serve as intracellular messengers to regulate transmembrane Ca2+ movements, Ca2+-dependent membrane transport functions, and other Ca2+- and polyamine-sensitive processes in cardiac myocytes.  相似文献   

3.
Apoptotic cell death of cardiomyocytes is involved in several cardiovascular diseases including ischemia, hypertrophy, and heart failure. The polyamines putrescine, spermidine, and spermine are polycations absolutely required for cell growth and division. However, increasing evidence indicates that polyamines, cell growth, and cell death can be tightly connected. In this paper, we have studied the involvement of polyamines in apoptosis of H9c2 cardiomyoblasts in a model of simulated ischemia. H9c2 cells were exposed to a condition of simulated ischemia, consisting of hypoxia plus serum deprivation, that induces apoptosis. The activity of ornithine decarboxylase, the rate limiting enzyme of polyamine biosynthesis that synthesizes putrescine, is rapidly and transiently induced in ischemic cells, reaching a maximum after 3 h, and leading to increased polyamine levels. Pharmacological inhibition of ornithine decarboxylase by alpha-difluoromethylornithine (DFMO) depletes H9c2 cardiomyoblasts of polyamines and protects the cells against ischemia-induced apoptosis. DFMO inhibits several of the molecular events of apoptosis that follow simulated ischemia, such as the release of cytochrome c from mitochondria, caspase activation, downregulation of Bcl-xL, and DNA fragmentation. The protective effect of DFMO is lost when exogenous putrescine is provided to the cells, indicating a specific role of polyamine synthesis in the development of apoptosis in this model of simulated ischemia. In cardiomyocytes obtained from transgenic mice overexpressing ornithine decarboxylase in the heart, caspase activation is dramatically increased following induction of apoptosis, with respect to cardiomyocytes from control mice, confirming a proapoptotic effect of polyamines. It is presented for the first time evidence of the involvement of polyamines in apoptosis of ischemic cardiac cells and the beneficial effect of DFMO treatment. In conclusion, this finding may suggest novel pharmacological approaches for the protection of cardiomyocytes injury caused by ischemia.  相似文献   

4.
BACKGROUND/AIMS: Hepatocyte growth factor and transforming growth factor-alpha are growth factors with important roles in hepatocyte proliferation. The polyamines, putrescine, spermidine, and spermine are widely distributed in many different cells and play an essential role in cell growth and differentiation. The present study examined the role of polyamine in this growth promoting factor-induced hepatocyte proliferation, in primary cultured rat hepatocytes. METHODOLOGY: Hepatocytes were isolated from rats by the collagenase perfusion method. Ornithine decarboxylase and S-adenosylmethionine decarboxylase activities were measured as the release of 14CO2 from L-[-14C]ornithine and S-adenosyl-L-[carboxyl14C]methionine, respectively. The concentration of polyamine was analyzed by high performance liquid chromatography. RESULTS: When transforming growth factor-alpha and hepatocyte growth factor were added to the hepatocyte culture simultaneously, ornithine decarboxylase activity, S-adenosylmethionine decarboxylase activity, polyamine concentration and DNA synthesis increased additively. The increase in DNA synthesis caused by transforming growth factor-alpha, hepatocyte growth factor, or both was completely inhibited by alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone). The inhibition was reversed by exogenous spermidine or spermine, but not by putrescine. CONCLUSIONS: Increased spermidine or spermine levels are essential for hepatocyte proliferation in cultured rat hepatocytes.  相似文献   

5.
We demonstrate that testosterone and its active metabolite 5alpha-dihydrotestosterone acutely (approximately 30 min) potentiate mouse ileal, but not duodenal, muscle activity. Androgens augment the amplitude of spontaneous peak-to-peak oscillations, alter the spontaneous activity frequency spectrum, and increase the amplitude of calcium-induced and carbachol-induced contractions. Concentration-dependence analyses revealed that maximal potentiation (449-910%) occurred at physiological concentrations of androgens (100 pM to 10 nM) with EC50 values in the picomolar range (8-20 pM). Western blot analyses using an antiandrogen receptor (anti-AR) antibody revealed the presence of two different AR proteins migrating at 87 and 110 kDa in ileal, but not duodenal, extracts. Androgen-induced potentiation was prevented by preincubation with AR antagonists flutamide or cyproterone acetate but was unaffected by pretreatment with cycloheximide plus actinomycin D, indicating that potentiation was mediated by ARs via a novel nongenomic mechanism. Androgen effects were mimicked by polyamines putrescine and spermine and were blocked by the ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase inhibitors alpha-difluoromethylornithine and berenil, respectively. Accordingly, androgens increase alpha-difluoromethylornithine-sensitive ornithine-decarboxylase- mediated L-ornithine decarboxylation in ileal tissues within the same time course as isometric potentiation. Both putrescine and dihydrotestosterone induced Ca2+ sensitization of ionomycin-permeabilized ileal smooth muscle. Finally, inhibition of the Rho kinase (ROK) pathway with the specific inhibitor Y27632 completely prevented androgen-induced potentiation. In agreement, androgens elicited ROK-induced Ser19 phosphorylation of myosin light chain 2 in ileal muscle. These data indicate that androgens potentiate ileal contractile activity by an AR-dependent nongenomic mechanism involving intracellular polyamine signaling and Ca2+ sensitization via ROK activation.  相似文献   

6.
This study was performed to determine if an alteration in vascular polyamine contents is associated with the development of deoxycorticosterone acetate-salt hypertension. The effects of chronic administration of alpha-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase and thus polyamine biosynthesis, on vascular polyamine contents, structure, and function as well as the development of hypertension was studied. Control and deoxycorticosterone acetate-salt rats received either tap water or a drinking solution containing alpha-difluoromethylornithine for 6 weeks, during which period systolic blood pressures were recorded. Vascular reactivity studies were performed on rings of aorta and tail artery. Medial thickness, vessel weight, and vascular polyamine contents were also assessed in these arteries. alpha-difluoromethylornithine treatment had no significant effect on either systolic blood pressure or vascular structure, function, and polyamine contents of control animals. The elevation in blood pressure and the increase in medial thickness, ring weight, and vascular polyamine contents as well as altered vascular reactivity observed in deoxycorticosterone acetate-salt rats was significantly attenuated by alpha-difluoromethylornithine treatment. These results are the first to demonstrate that vascular polyamine contents are elevated in the deoxycorticosterone acetate-salt rat and that chronic alpha-difluoromethylornithine treatment prevents the rise in vascular polyamines as well as the elevation in blood pressure and attendant changes in the vasculature. Thus, the increase in vascular polyamines may comprise a critical link between the initiating stimuli and the alterations in vascular structure and function implicated in the pathogenesis of deoxycorticosterone acetate-salt hypertension.  相似文献   

7.
This investigation shows whether polyamines and ornithine decarboxylase have a role in duodenal mucosal repair following stress-induced microscopic damage. Rats were fasted for 22 hours, placed in restraint cages, and immersed in water to the xiphoid process for 6 hours. Animals were killed either immediately after the period of stress or at 2-hour intervals up to 24 hours thereafter. Duodenal mucosa was examined histologically, and ornithine decarboxylase and polyamine levels were measured. Ornithine decarboxylase activity was increased significantly up to 6 hours following stress, peaking at 4 hours at a level 10 times the prestress control. By 8 hours, enzyme activity had returned to near normal. Increases in mucosal putrescine, spermidine, and spermine content paralleled the changes in ornithine decarboxylase activity and peaked 4 hours after stress. Stress resulted in microscopic damage evidenced by a nearly complete absence of villi. Significant macroscopic lesions were not present following stress. Mucosal repair was evident 12 hours after stress and almost complete by 24 hours, although the restituted villi were short and blunted. The decreases in mucosal DNA, RNA, and protein content caused by stress were restored and reached near-normal levels 12 hours after the period of stress. In animals given the specific inhibitor of ornithine decarboxylase, alpha-difluoromethylornithine, increases in duodenal mucosal ornithine decarboxylase activity and polyamine levels were inhibited and mucosal repair was almost completely prevented following stress. alpha-Difluoromethylornithine also prevented the recovery of DNA, RNA, and protein content of the duodenal mucosa. These results indicate that duodenal mucosal damage following stress is repaired rapidly; the repair process is accompanied by significant increases in ornithine decarboxylase activity and polyamine levels; and the increases in ornithine decarboxylase and polyamines are absolutely required for the normal repair of the mucosa.  相似文献   

8.
Escherichia coli K-12 mutants that carry deletions in their genes for ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) (speC), arginine decarboxylase (L-arginine carboxy-lyase, EC 4.1.1.19) (speA), and agmatine ureohydrolase (agmatinase or agmatine amidinohydrolase, EC 3.5.3.11) (speB) can still synthesize very small amounts of putrescine and spermidine. The putrescine concentration in these mutants was found to be 1/2500th that in spe+ cells. The pathway of putrescine synthesis appears to be through the biodegradative arginine decarboxylase, which converts arginine to agmatine, in combination with a low agmatine ureohydrolase activity--1/2000th that in spe+ strains. These results suggest that even such low levels of polyamines permit a low level of protein synthesis. Evidence is presented that the polyamine requirement for the growth of the polyamine-dependent speAB, speC deletion mutants, which are also streptomycin resistant, is not due to a decreased ability to synthesize polyamines.  相似文献   

9.
DFMO is a selective irreversible inhibitor of ornithine decarboxylase (ODC), the initial enzyme in the polyamine biosynthetic pathway. DFMO was utilized to determine the role of polyamines in isoproterenol (ISO)-induced cardiac hypertrophy. Daily subcutaneous administration of 200 mg/kg of DFMO reduced cardiac putrescine levels but did not significantly alter the basal levels of spermidine or spermine, nor was normal cardiac growth affected. ISO-induced cardiac hypertrophy was accompanied by increased putrescine and spermidine levels but spermine was not significantly altered. DFMO reversed the ISO-induced increases in putrescine and inhibited or attenuated both the increases in spermidine content and the cardiac hypertrophy. Although normal ODC activity appears not to be necessary for the maintenance of basal levels of polyamines or for normal cardiac growth, sustained inhibition of ODC interferes with ISO-induced elevations of putrescine, spermidine and heart weight.  相似文献   

10.
The human promyelocytic leukemia cell line, HL-60, differentiated into macrophage/monocytes in the presence of 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3], as assessed by the percentage of morphologically mature cells and their ability to reduce nitroblue tetrazolium. In this study of the mechanism involved, the activities of ornithine decarboxylase and spermidine/spermine-N1-acetyltransferase (SAT), the rate-limiting enzymes of polyamine metabolism, as well as the cellular levels of polyamine were measured. ODC activity reached a peak 24 h after the addition of 1 alpha,25(OH)2D3 and then decreased, while SAT activity gradually increased as differentiation commenced. An increase in putrescine and decreases in spermidine and spermine were also observed. Addition of alpha-difluoromethylornithine, an irreversible inhibitor of ODC, with or without methylglyoxalbis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, caused no effect on 1 alpha,25(OH)2D3-induced cell differentiation, although the cellular levels of putrescine and spermidine decreased markedly. Addition of alpha-difluoromethylornithine markedly suppressed cell proliferation; this effect was reversed by the addition of exogenous putrescine. Addition of exogenous spermidine or spermine to overcome activation of SAT also had no effect on 1 alpha,25(OH)2D3-induced cell differentiation. These results suggest both that polyamine metabolism is not important in 1 alpha,25(OH)2D3-induced differentiation of HL-60 cells, but that it is intimately involved in the proliferation of these cells.  相似文献   

11.
Polyamine metabolism in Pneumocystis carinii   总被引:1,自引:0,他引:1  
Alpha-difluoromethylornithine (DFMO) is being used to treat Pneumocystis carinii pneumonia despite a lack of in vitro evidence supporting its antipneumocystis activity. DFMO is a specific inhibitor of ornithine decarboxylase, the rate-limiting enzyme of polyamine biosynthesis. To investigate polyamine metabolism in P. carinii, extracts of the organism were analyzed for polyamine content and ornithine decarboxylase activity, and [3H]ornithine and [14C]arginine incorporation into polyamines during short-term culture was determined. P. carinii extracts contained putrescine and spermidine in a ratio of 0.17:1; traces of spermine were detected. Although ornithine decarboxylase activity was not detected, P. carinii incorporated ornithine and arginine into putrescine and spermidine but not into spermine, suggesting that the spermine detected derived from contaminating host cells. Uninfected rat lung incorporated ornithine minimally. Pentamidine, DFMO, and alpha-monofluoromethyldehydroornithine methyl ester inhibited ornithine incorporation by up to 86% at clinically achievable concentrations. These data provide a rationale for using polyamine synthesis antagonists in P. carinii pneumonia and a method for screening antipneumocystis drugs in vitro.  相似文献   

12.
This study was designed to investigate changes of ornithine decarboxylase and polyamines during pancreatic adaptation in response to feeding of the synthetic protease inhibitor camostate. alpha-Difluoromethylornithine, an irreversible and specific inhibitor of ornithine decarboxylase, was applied simultaneously to elucidate the essential role of polyamines in pancreatic growth. Cholecystokinin (CCK) plasma levels in camostate-fed rats increased from basal values of 3-4 pmol/l to a maximal level of 27.4 pmol/l after 2h; they then decreased up to 12 h but remained elevated above controls throughout the 30-day experiments. In the camostate group pancreatic ornithine decarboxylase activity was elevated after 2 h, reaching a maximum after 6 h (1,858.5 pmol 14CO2/h/mg DNA, about 200-fold above controls) followed by a significant increase in putrescine after 4 h and spermidine after 24 h while spermine remained unchanged. The trophic parameters increased in the following time sequence: thymidine kinase (12 h), DNA polymerase (12 h), protein (24 h), pancreatic weight (24 h) and DNA (5 days). alpha-Difluoromethylornithine significantly delayed and reduced the camostate-induced increase in ornithine decarboxylase activity and polyamine concentrations as well as the trophic parameters. Application of the CCK receptor antagonist L-364,718 resulted in complete inhibition of the increases in ornithine decarboxylase, polyamines and all trophic parameters. These data indicate an important role for ornithine decarboxylase and polyamines in camostate-induced pancreatic growth and hormonal mediated pancreatic adaptation in rats.  相似文献   

13.
In Escherichia coli, the biosynthetic ornithine and arginine decarboxylases (EC 4.1.1.17 and 4.1.1.19, respectively) are responsible for the biosynthesis of polyamines from ornithine and arginine, respectively. When E. coli cells are grown in the presence of increasing amounts of polyamines, a progressive increase in the amount of antizyme 1 and antizyme 2 occurs. The amino acid compositions of antizymes 1 and 2 show them to be basic proteins; antizyme 1 has an amino acid composition similar to that of the E. coli histone-like protein HU and of the eukaryotic histone H2B; antizyme 2 is characterized by an unusually high arginine content. We find these proteins to be specific inhibitors of both the biosynthetic ornithine decarboxylase and the biosynthetic arginine decarboxylase. They do not inhibit the corresponding biodegradative ornithine and arginine decarboxylases, nor do they inhibit lysine decarboxylase or S-adenosylmethionine decarboxylase. These properties of the antizymes favor their function in the regulation of polyamine biosynthesis in E. coli. The ability of the purified antizymes to inhibit the ornithine and arginine decarboxylases is stabilized in acidic buffers and is lost upon prolonged exposure to solutions at neutral or basic pH.  相似文献   

14.
Chicks with genetically elevated renal arginase activity were fed crystalline amino acid diets varying in ornithine concentration (0, 1 or 2%) to assess the potential for precursor regulation of polyamine synthesis. Renal arginase and renal and hepatic ornithine decarboxylase activities fell when ornithine was fed. Renal and hepatic ornithine concentrations rose while putrescine concentrations varied quadratically with ornithine feeding. Spermidine and spermine concentrations were not affected by diet. It was concluded that ornithine synthesized in vivo was a more potent stimulator of polyamine synthesis than ornithine of dietary origin.  相似文献   

15.
16.
Putrescine is involved in the vitamin D action in chick intestine   总被引:1,自引:0,他引:1  
We have reported that a single injection of 1 alpha,25-dihydroxyvitamin D3 into vitamin D-deficient chicks produces a marked increase of putrescine accumulation in the duodenum from two different sources, ornithine and spermidine. In the present study, the effects of putrescine depletion and its supplementation on duodenal villus length and calcium absorption were examined in newborn and 5-week-old chicks. Administering either alpha-difluoromethylornithine, a specific inhibitor of ornithine decarboxylase, or N1,N4-bis(2,3-butadienyl)-1,4-butanediamine, a specific inhibitor of polyamine oxidase, to newborn chicks significantly decreased the duodenal content of putrescine and calcium transport activity. The putrescine depletion also induced shortening of the duodenal villus length. The inhibition of calcium absorption and villus length in the putrescine-depleted chicks was almost completely restored by administering putrescine to the birds. The effect of the putrescine depletion and its supplementation on the duodenal villus length and the calcium absorption was reproduced in 5-week-old vitamin D-deficient chicks given vitamin D3 or 1 alpha,25-dihydroxyvitamin D3. These results clearly indicate that putrescine is somehow involved in the vitamin D action in maintaining the morphological and functional development of the intestinal villus mucosa.  相似文献   

17.
12-O-Tetradecanoyl phorbol-13-acetate (TPA), a tumor promoter, stimulates DNA synthesis in mouse epidermal cells in vivo and in vitro. This response appears to be mediated through polyamine metabolism because ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17)activity is markedly increased shortly after promoter exposure and this induction varies in magnitude according to dose and promoter potency of a series of phorbol esters. In vitro, exogenous putrescine (0.01-10 mM) results in a dose-related increase and prolongation of promoter-stimulated DNA DNA synthesis, a phenomenon noted in other systems of polyamine-mediated growth stimulation. The anti-inflammatory steroid fluocinolone acetonide (FA), an inhibitor of tumor promotion, prevents TPA stimulation of epidermal proliferation in vivo and in vitro. In vitro, FA most effectively prevents stimulation of DNA synthesis when applied is not required. Paradoxially, FA potentiates the increase in ornithine decarboxylase activity after TPA administeration both in vivo and in vitro. Furthermore, the inhibition of TPA-stimulated DNA synthesis by FA in vitro can be reversed by exogenous putrescine. These results suggestthat FA exerts its antipromotion effect by reducing the sensitivity of the cell to polyamines or by reducing intracellular polyamine levels.  相似文献   

18.
Mucosal polyamine metabolism in the columnar lined oesophagus.   总被引:1,自引:0,他引:1       下载免费PDF全文
Mucosal ornithine decarboxylase activity and polyamine content has been proposed as a possible marker for malignant potential in gastrointestinal mucosa. Polyamine content and histological findings were examined in 107 pairs of endoscopic biopsy specimens taken from gastric fundus, fundic and specialised Barrett's oesophagus and Barrett's adenocarcinoma. The content of putrescine (median nmol/mg protein, range) the primary product of ornithine decarboxylase showed a progressive increase from gastric fundus (0.41, 0.15-1.5); fundic (0.45, 0.01-4.08); specialised Barrett's oesophagus (0.54, 0.01-2.0); dysplastic columnar lined oesophagus (0.56, 0.31-3.1) to adenocarcinoma (1.23, 0.29-8.98). Adenocarcinoma putrescine content was significantly greater than gastric fundus (p < 0.018) and fundic (p < 0.03). Mucosal spermine, spermidine, and total polyamine values were greater in gastric fundus than fundic, specialised Barrett's oesophagus, and dysplastic columnar lined oesophagus (all p < 0.001) suggesting failure to further metabolise putrescine to its higher polyamines in the metaplastic epithelium. Although metaplastic columnar lined oesophagus shows significant differences in polyamine metabolic activity from the stomach the important distinction between specialised and dysplastic columnar lined oesophagus cannot be made by measuring the polyamine content.  相似文献   

19.
AIM: To study the transepithelial transport characteristics of the polyamine putrescine in human intestinal Caco-2 cell monolayers to elucidate the mechanisms of the putrescine intestinal absorption. METHODS: The transepithelial transport and the cellular accumulation of putrescine was measured using Caco-2 cell monolayers grown on permeable filters. RESULTS: Transepithelial transport of putrescine in physiological concentrations (> 0.5 mM) from the apical to basolateral side was linear. Intracellular accumulation of putrescine was higher in confluent than in fully differentiated Caco-2 cells, but still negligible (less than 0.5%) of the overall transport across the monolayers in apical to basolateral direction.EGF enhanced putrescine accumulation in Caco-2 cells by four fold, as well as putrescine conversion to spermidine and spermine by enhancing the activity of S adenosylmethionine decarboxylase. However, EGF did not have any significant influence on putrescine flux across the Caco-2 cell monolayers. Excretion of putrescine from Caco-2 cells into the basolateral medium did not exceed 50 picomoles, while putrescine passive flux from the apical to the basolateral chamber, contributed hundreds of micromoles polyamines to the basolateral chamber. CONCLUSION :Transepithelial transport of putrescine across Caco2 cell monolayers occurs in passive diffusion, and is not influenced when epithelial cells are stimulated to proliferate by a potent mitogen such as EGF.  相似文献   

20.
Hormonal control of polyamine levels in bovine adrenocortical cells   总被引:1,自引:0,他引:1  
J J Feige  C Madani  E M Chambaz 《Endocrinology》1986,118(3):1059-1066
The implication of polyamines in cellular growth and differentiation processes and the existence of a polyamine-mediated protein phosphorylation system in adrenocortical cells suggest that polyamines may be examined as potential intracellular messengers in the pleiotypic action of ACTH. Bovine adrenocortical cells in culture exhibit a specific, energy-dependent, partly sodium-supported, inward polyamine transport system, independent of the A, L, and N aminoacid uptake systems. Steroidogenic concentrations of ACTH (10(-12) to 10(-9)M) induced a rapid activation of the polyamine uptake, resulting in a 2- to 3-fold increase in intracellular polyamine content, over 1 h. The ACTH dose-response curves for steroidogenic activity and for polyamine uptake were similar. Other adrenocortical effectors such as angiotensin II, acetylcholine, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) activated polyamine uptake with a pattern parallel to their steroidogenic potency (i.e. ACTH greater than angiotensin II greater than acetylcholine, TPA). Steroidogenic concentrations of 8-bromo-cAMP displayed no effect on the adrenocortical polyamine uptake, suggesting that cAMP does not mediate this action of ACTH. On the other hand, ACTH induced a large increase in ornithine decarboxylase (ODC) activity in bovine adrenocortical cells, after a 6- to 8-h lag period, resulting in an average 2-fold increase in cell putrescine, spermidine, and spermine content. However, when the cells were previously polyamine loaded, ACTH-dependent ODC induction was suppressed. Adrenocortical cell polyamine content thus appears to be under hormonal control. ACTH may act through two possible pathways: 1) the rapid activation of the cell polyamine accumulation from an extracellular source and 2) the delayed increase in polyamine biosynthesis secondary to induction of ODC activity, when the cells are relatively depleted of the polyamines. These observations suggest that polyamines may function as intracellular messengers for some of the ACTH effects in bovine adrenocortical cells.  相似文献   

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