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1.
Intestinal obstruction inhibits amino acid absorption. The inhibition, being dependent on the pathological changes of the absorptive epithelium, was considered as an index of injury and measured after varying periods of obstruction and after pretreatment with clindamycin, indomethacin, 16,16-dimethyl-PGE2 or arachidonic acid. A reduction in amino acid uptake was apparent after 2h of obstruction and was increasingly evident after 4, 6 and 18 h. During the late phase (after 6 h), inhibition was partly prevented by pretreatment with clindamycin, but the antibiotic was ineffective during the early phase (within the first 2 h). Bacterial colony counts of luminal contents of rats obstructed for 2 h, were not different from counts obtained in controls, but significantly lower than counts in rats that have been obstructed for 6 h. Pretreatment of rats with 16,16-dimethyl-PGE2 or with arachidonic acid prevented the early inhibitory effects of the obstruction. The findings suggest that the early inhibition in amino acid uptake may be related to metabolic changes that are correctable by the administration of 16,16-dimethyl-PGE2 or of arachidonic acid. The inhibition, during the late phase, is mainly related to an overgrowth of the enteric bacteria. 相似文献
2.
The aim of the present study was to investigate in late first trimester and early second trimester patients whether whole cell homogenates of cervical tissue incubated with 14C-arachidonic acid was affected by pretreatment for 12 to 14 hours with PGE2 and 9-deoxo- 16,16-dimethyl-9-methylene PGE2 (9-methylene PGE2). After extraction, purification and separation, identification of the compounds found during incubation was achieved using radio-gas liquid chromatography and gas-liquid chromatography-mass spectrometry. Treatment with 9-methylene PGE2 accomplished a reduced production of 14C-labelled PGF2 alpha, -PGE2 and TxB2, while pretreatment with PGE2 induced increase in the production of 14C-6-keto-PGF1 alpha when cervical tissue homogenates were compared with specimens obtained from non-pretreated patients. Recently we reported a significantly increased formation of so far unidentified metabolite(s) in homogenates of human cervical tissue specimens obtained at or near term when compared with corresponding specimens obtained during early pregnancy. With both types of prostaglandin pretreatment there was a tendency of increased formation of these metabolites. It seems possible that the influence on the biochemistry of cervical tissue induced by PGE2 and 9-methylene PGE2 is mediated via the endogenous arachidonic acid cascade towards non-prostaglandin compound(s). 相似文献
3.
B M Chapnick 《Canadian journal of physiology and pharmacology》1984,62(6):689-694
In anesthetized dogs 48 h after unilateral ureteral ligation, intra-arterial injection of arachidonic acid produced a transient increase followed by a prolonged decrease of resistance in the ureteral-ligated kidney; whereas, in the control kidney, only the prolonged decrease in resistance was observed in response to arachidonate. Indomethacin blocked not only the arachidonate-induced renal efflux of both immunoreactive 6-keto-prostaglandin F1 alpha and thromboxane B2 but also vasodilation in both kidneys. In contrast, the initial vasoconstriction in the obstructed kidney was not affected by pretreatment with the cyclo-oxygenase inhibitor. Infusion of 5,8,11,14-eicosatetraynoic acid, an inhibitor of lipoxygenase activity, into the ureteral-ligated kidney after indomethacin markedly reduced the initial vasoconstrictor response to arachidonate. These data demonstrate that vascular reactivity to arachidonic acid is altered in the ureteral-obstructed kidney and are consistent with the hypothesis that formation of lipoxygenase as well as cyclooxygenase derivatives may participate in the hemodynamic responses to arachidonic acid in this pathophysiologic model. 相似文献
4.
Daily intratumor administration of 16,16-dimethyl-PGE2-methyl ester in two different dosages inhibited tumor growth in C57Bl/6J mice bearing subcutaneous B-16 melanomas. The larger dose (20 microgram/day/mouse) produced a 68% decrease in tumor volume, a 69% decrease in tumor weight and a 60% decrease in the number of cells in mitotic phase. The smaller dose (10microgram/day/mouse) was one fifth less effective than the 20microgram dose but produced similar changes. Histological examination of tumors revealed no significant differences either in the inflammatory cell population or the amount of necrosis in the control and di-M-PGE2-treated tumors. 相似文献
5.
Some (+)-11-deoxy-16-phenoxyprostaglandin E1 analogues have been evaluated as uterine stimulants in the anaesthetised pregnant rat. Gastrointestinal side effects, assessed by the antagonism of morphine-induced constipation in the mouse, were relatively low with some of these compounds, six of which had a much more favourable relative selectivity than 16,16-dimethyl-PGE2 methyl ester. 相似文献
6.
Regulation of cyclic AMP metabolism in rabbit cortical collecting tubule cells by prostaglandins 总被引:6,自引:0,他引:6
Prostaglandin E1 (PGE1) at 1 nM inhibits arginine-vasopressin (AVP)-induced water reabsorption in the rabbit cortical collecting tubule (RCCT), while 100 nM PGE1, by itself, stimulates water reabsorption (Grantham, J. J., and Orloff, J. (1968) J. Clin. Invest. 47, 1154-1161). To investigate the basis for these two responses, we measured the effects of prostaglandins on cAMP metabolism in purified RCCT cells. In freshly isolated cells, PGE2, PGE1, and 16,16-dimethyl-PGE2 acting at high concentrations (0.1-10 microM) stimulated cAMP accumulation; however, one PGE2 analog, sulprostone (16-phenoxy-17,18,19,20-tetranor-PGE2 methylsulfonilamide), failed to stimulate cAMP accumulation or to antagonize PGE2-induced cAMP formation; PGD2, PGF2 alpha, and a PGI2 analog, carbacyclin (6-carbaprostaglandin I2), also failed to stimulate cAMP synthesis. These results suggest that there is a PGE-specific stimulatory receptor in RCCT cells which mediates activation of adenylate cyclase. Occupancy of this receptor would be anticipated to cause water reabsorption by the collecting tubule. At lower concentrations (0.1-100 nM) PGE2, PGE1, 16,16-dimethyl-PGE2, and, in addition, sulprostone inhibited AVP-induced cAMP accumulation by fresh RCCT cells in the presence of cAMP phosphodiesterase inhibitors. Pertussis toxin pretreatment of RCCT cells blocked the ability of both PGE2 and sulprostone to inhibit AVP-induced cAMP accumulation. In membranes prepared from RCCT cells, sulprostone prevented stimulation of adenylate cyclase by AVP. These results suggest that E-series prostaglandins (including sulprostone) can act through an inhibitory PGE receptor(s) coupled to the inhibitory guanine nucleotide regulatory protein, Gi, to block AVP-induced cAMP synthesis by RCCT cells. Occupancy of this receptor would be expected to cause inhibition of AVP-induced water reabsorption in the intact tubule. Curiously, after RCCT cells were cultured for 5-7 days, PGE2 no longer inhibited AVP-induced cAMP accumulation, but PGE2 by itself could still stimulate cAMP accumulation. In contrast to PGE2, epinephrine acting via an alpha 2-adrenergic, Gi-linked mechanism did block AVP-induced cAMP formation by cultured RCCT cells. This implies that some component of the inhibitory PGE response other than Gi is lost when RCCT cells are cultured. 相似文献
7.
The effect of partial outlet obstruction on prostaglandin generation in the rabbit urinary bladder 总被引:3,自引:0,他引:3
Partial outlet obstruction of the urinary bladder has been demonstrated to induce specific dysfunctions in cellular and sub-cellular membrane structures within the bladder's smooth muscle and mucosal compartments. Recent studies have linked these membrane dysfunctions to alterations in phospholipid metabolism leading to mobilization of free arachidonic acid, the precursor for synthesis of prostaglandins (PG). The purpose of this study was to determine if partial outlet obstruction of the urinary bladder induces changes in the capacity of bladder smooth muscle and mucosa to generate PG. PG were isolated from control and partially obstructed urinary bladder smooth muscle and mucosa of male New Zealand White (NZW) rabbits. PG concentrations (PGE2, PGF2alpha and PGI2, as its stable metabolite 6-keto-PGF1alpha) were determined after 30 minute incubations using enzyme-linked immunoassay (ELISA) kits. In both control and obstructed rabbit urinary bladders, PG generation was significantly higher in isolated mucosa than muscle tissues. A significantly higher concentration of PGF2alpha, and 6-keto-PGF1alpha was measured in obstructed muscle tissue relative to controls. The concentration of 6-keto-PGF1alpha was also significantly higher than the concentrations measured for PGE2 and PGF2alpha in both control and obstructed smooth muscle samples. The generation of PGE2 was significantly higher in rabbit urinary bladder mucosa than either PGF2alpha or 6-keto-PGF1alpha in both control and obstructed samples. The capacity of obstructed mucosal tissue to generate 6-keto-PGF1alpha was significantly higher than control tissue, while no significant differences in PGE or PGF2alpha generation were noted. These data suggest obstruction of the urinary bladder induce specific elevations in PG in both smooth muscle and mucosal tissues. 相似文献
8.
Effect of pulmonary oedema induced by alpha-naphthylthiourea on synthesis of cyclo-oxygenase products in rat isolated lungs 总被引:2,自引:0,他引:2
Synthesis of COP (prostaglandins; PG and thromboxanes; Tx) from exogenous and endogenous arachidonic acid (AA) was studied in isolated perfused lungs from rats treated in vivo with a single dose of alpha-naphthylthiourea (ANTU; 10mg/kg;). Lung dry:wet weight ratios showed changes characteristic of oedema between 6 and 16h after ANTU. Bioassay of COP showed that COP synthesis from exogenous AA was raised above control values in lungs from rats treated with ANTU, reaching a maximum at 16h after treatment. By radioimmunoassay, the major increase was in 6-oxo-PGF1 alpha, with lesser effects on PGE2 and PGF2 alpha levels. Synthesis of bioassayable COP from endogenous AA induced by the calcium ionophore A23187 was increased as early as 2h after ANTU treatment and remained elevated up to 70h. In lungs 28h after ANTU, 6-oxo-PGF1 alpha release was greater than in normal lungs. These results show that in this model of pulmonary oedema, the potential for COP synthesis was increased. From the time course of this effect, increased COP synthesis was probably a response to the initial damage rather than a cause of the oedema. 相似文献
9.
Shibani Chaudhury Marie Martin Jeremiah F. Payne Anver Rahimtula 《Journal of biochemical and molecular toxicology》1987,2(2):93-104
Administration of a Prudhoe Bay crude oil (PBCO) to rats has been shown to (a) inhibit platelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid, or epinephrine and (b) induce benzo-α-pyrene hydroxylase (BPH) in the liver and small intestine. Maximum inhibition of aggregation (90%) was seen 12 to 16 hours subsequent to dosing. However, substantial inhibition was observed as early as four hours and as late as 48 hours after dosing. Of particular interest was the sensitivity of the platelet response compared with the putatively sensitive response of monooxygenase induction in liver. As little as 0.1 ml of PBCO per kilogram body weight (bw) caused an inhibition of aggregation with all three agonists. A similar inhibition of the release of ADP from platelets in the presence of arachidonic acid or epinephrine was also observed. In contrast, hepatic BPH activity showed only a modest increase (67%) over the control value even after administration of 2 ml of PBCO per kilogram body weight. Small intestine BPH activity was more sensitive, showing a gradual increase of up to 19-fold 24 hours after dosing with 2 ml of PBCO per kilogram body weight. The sensitivity of the platelet response is of general environmental interest and evaluating platelet aggregation in humans may be important as a noninvasive assay for exposure to either accidental or “acceptable” levels of petroleum hydrocarbons in the occupational environment. 相似文献
10.
The in vivo monkey uterine stimulating potency of 9-deoxy-16,16-dimethyl-9-methylene-PGE2 is similar to that of 16,16-dimethyl-PGE2 and approximately 15 times that of PGE2. Low doses of this compound stimulated uterine contractions when administered vaginally. Pregnancy was terminated prematurely following subcutaneous, intramuscular or vaginal suppository treatment. Estimates of potential for gastrointestinal side effects using the rat enteropooling assay and in vivo monkey effects indicate that diarrhea will be substantially reduced with retention of uterine stimulating potency. 相似文献
11.
Bocanegra V Rinaldi Tosi M Gil Lorenzo A Cacciamani V Manucha W Fornés M Vallés PG 《Histology and histopathology》2012,27(7):919-930
Intrarenal renin-Angiotensin system (RAS) activity is increased during early development and is further enhanced by unilateral ureteral obstruction (UUO). We studied the involvement of mitogen-activated protein (MAP) kinase members and the RhoA GTPase signaling pathways on the regulation of renal cell response after AT1 Angiotensin II receptor inhibition in obstruction. Neonatal rats subjected to sham operation or complete UUO within the first 48 hours of life received saline vehicle, Losartan (AT1 inhibitor), or PD-123319 (AT2 inhibitor) during the first 14 days of life. Cortex tubular epithelial cell apoptotic response was shown by TUNEL and confirmed by electron microscopy associated with mitochondrial signaling pathway through the increased proapoptotic ratio Bax/BcL-2, and consequently increased caspase 3 expression and activity in obstructed kidney before and after Type 1 (AT1) receptor blockade. Non injury of contralateral kidney was shown. The convergence of two independent signal pathways, the RhoA GTPase and pERK and concurrent inhibition of JNK MAP kinase, were required for the apoptotic response in 14 day kidney obstructed tubular cells either with or without Losartan treatment. Absence of increased AT2 protein expression after AT1 receptor inhibition on day 14 of obstruction was shown. Selective AngiotensinAT2-receptor inhibition with PD-123319 had no protective effect on the renal response to complete 14 day UUO. We suggest a role of both RhoA GTPase activation and the opposing actions of the ERK and JNK-MAP kinase signaling pathways as events involved in tubular cell apoptosis regulation in neonatal UUO. The selective AT1-receptor inhibition had no effect on the renal cellular response in the kidney subjected to UUO for 14 days. 相似文献
12.
The aim of this study was to investigate mechanisms responsible for the inhibition of biliary glutathione efflux in rats with secondary biliary cirrhosis. Rats were studied after bile duct obstruction for 28 days. The biliary secretion of reduced glutathione (GSH), oxidised glutathione (GSSG) and cysteine were completely inhibited in biliary obstructed rats. Hepatic gamma glutamyltranspeptidase (gamma-GT) activity increased significantly, but following its inhibition by acivicin administration GSH, GSSG and cysteine were still absent in bile. Biliary obstruction resulted in a significant increase of the permeability of the paracellular pathway, as shown by the higher bile/plasma ratio and hepatic clearance of [14C]sucrose. GSH and GSSG were, however, significantly lower in the carotid artery and hepatic vein of obstructed animals and the arteriovenous difference across the liver was reduced. The concentration of GSH was significantly reduced and that of GSSG increased in the liver of obstructed rats. Biliary obstruction induced an increase in the hepatic concentration of cysteine and an inhibition of both gamma glutamylcysteine synthetase and methionine adenosyl transferase activities. Dichlorofluorescein (DCF) and the GSSG/GSH ratio and thiobarbituric acid reactive substances (TBARS) concentration, markers of reactive oxygen species production and lipid peroxidation, respectively, were significantly increased. Our data indicate that increased degradation or blood reflux of glutathione do not participate in the disruption of its secretion into bile and support the view that impairment of glutathione synthesis and oxidative stress could contribute to the decline in biliary glutathione output. 相似文献
13.
Prostaglandin D2 was found to be a potent inhibitor of B-16 melanoma cell replication . The inhibition was dose-dependent between 3×10?9M and 3×10?6M (IC50~ 0.3 μM after 6 days). On a molar basis, PGD2 was a better inhibitor than PGA2 or 16,16-dimethyl-PGE2-methyl ester (di-M-PGE2) and in higher concentrations (10?6?10?7M), comparable to retinoic acid. In higher concentrations, PGD2 inhibited DNA, RNA and protein synthesis. The B-16 melanoma cell line which we used synthesized arachidonic acid metabolites which comigrated with PGA2, PGD2, PGE2 and PGF2α on a thin layer chromatography system. 相似文献
14.
Epidermal growth factor and prostaglandin E(2) accelerate mucosal recovery from stress-induced gastric lesions via inhibition of apoptosis. 总被引:15,自引:0,他引:15
P C Konturek T Brzozowski A Duda S Kwiecien S L?ber A Dembinski E G Hahn S J Konturek 《Journal of Physiology》2001,95(1-6):361-367
The repair of damaged gastric mucosa is a complex process involving prostaglandins (PG) and mucosal growth factors such as epidermal growth factor (EGF). Recently, we postulated that the increased occurrence of apoptosis in the gastric epithelium might be of pathophysiological importance in the development of stress lesions. The aim of the present study was to assess the effect of the pretreatment of rats, exposed to 3.5 h of water immersion and restraint stress (WRS), with EGF and PG (16,16 dmPGE(2)) on the number of stress lesions, recovery of gastric mucosa from stress and the expression of apoptosis related genes such as caspase-3 and antiapoptotic bcl-2. Rats were divided in following groups: (1) vehicle; (2) EGF 100 microg/kg i.p.; (3) 16,16 dm-PGE(2) (5 microg/kg i.g.) and caspase-1 inhibitor (ICE-I; 100 microg/kg i.p.). One hour later, the rats were exposed to 3.5 h of WRS and then sacrificed immediately (0 h) or at 6, 12, or 24 h after WRS. The number of acute gastric lesions was determined. Gastric epithelial apoptosis was assessed by TUNEL staining. In addition, mRNA expression of caspase-3, Bcl-2 and proinflammatory cytokines (IL-1 beta, TNFalpha) was assessed by RT-PCR. PGE(2) generation in gastric mucosa and luminal EGF were determined by RIA. Exposure to WRS resulted in the development of multiple acute stress erosions ( approximately 18) which almost completely healed during 24 h. The gastric blood flow was significantly reduced (approximately 70% of intact mucosa) immediately after WRS. The expression of mRNA for IL-1 beta and TNF alpha reached their peak at 12 h after stress exposure. The apoptosis rate was highest at 6 h after WRS and was accompanied by the highest caspase-3 expression. In rats pretreated with EGF or 16,16 dm-PGE(2), a significant decrease in caspase-3 mRNA and upregulation of bcl-2 mRNA as observed as compared to vehicle controls. Caspase-1 inhibitor significantly reduced the number of stress lesions. We conclude that EGF and PGE(2) accelerate healing of stress-induced lesions due to the attenuation of apoptosis via upregulation of bcl-2 in gastric mucosa. Inhibitors of apoptosis accelerate healing of stress lesions and may be potentially effective agents in the healing of damaged gastric mucosa. 相似文献
15.
TPA regulation of prostaglandin H synthase activity in primary and subcultured dog urothelial cells was investigated. Previous studies have demonstrated an early (0-2 hr) increase in PGE2 synthesis mediated by TPA which is dependent upon release of endogenous arachidonic acid by a phospholipase-mediated pathway. In this study, prostaglandin H synthase activity was assessed directly with microsomes and indirectly after addition of exogenous arachidonic acid at a maximum effective concentration (100 microM) to media. PGE2 synthesis, measured by radioimmunoassay, served as an index of prostaglandin H synthase activity. After a 24-hr incubation with 0.1 microM TPA or 1.0 microM A23187, arachidonic acid elicited significantly more PGE2 synthesis in agonist-treated cells than it did in control cells in primary culture. Microsomes from 24-hr TPA-treated cells exhibited significantly more prostaglandin H synthase activity than did those from control cells. In addition, the PGE2 content of overnight media was approximately 10-fold greater in TPA-treated cells than in control cells. The late (24 hr) response was more sensitive to lower concentrations of TPA than was the earlier (0-2 hr) response. TPA at 0.1 microM was a maximum effective dose for both responses. The 24-hr response was blocked by cycloheximide and staurosporine, inhibitors of protein synthesis and protein kinase C, respectively. Pretreatment of cells with aspirin, an irreversible inhibitor of prostaglandin H synthase, prior to addition of TPA did not prevent the late TPA-mediated increase in PGE2 synthesis. Subcultured cells exhibited both an early and a late TPA response. Only the early response was inhibited by aspirin pretreatment. Results suggest that the late response with TPA is caused by de novo synthesis of prostaglandin H synthase. Thus, primary and subcultured dog urothelial cells possess two distinct mechanisms for regulating signal transduction by arachidonic acid metabolism. This study provides a basis for assessing these mechanisms of signal transduction in urothelial cell lines and transformed cells. 相似文献
16.
The radioprotection by several eicosanoids was investigated in cultures of bovine aortic endothelial cells. One hour before irradiation (0-500 cGy, 137Cs gamma rays) 10 micrograms/ml of PGD2, PGE1, PGI2, misoprostol (PGE1-analog), 16,16-dimethyl PGE2, PGA2, or 1 microgram/ml LTC4 was added. Radiation decreased incorporation of [3H]thymidine at 4 h, cell number/culture at 24 h, and cell survival as measured by colony formation. Under these conditions the eicosanoids were not radioprotective. Two eicosanoids, PGD2 and PGA2, appeared to be toxic. Because receptors might mediate eicosanoid-induced radioprotection, radioligand binding of PGE2 and LTC4 and levels of adenosine 3',5'-cyclic monophosphate (cAMP) were measured. Evidence for a receptor was equivocal; there was nonspecific binding and metabolism of LTC4. The level of cAMP was elevated by 16-16-dimethyl-PGE2 in the presence of isobutyl methylxanthine; however, this combination of the prostaglandin and the methylxanthine was not radioprotective. These investigations suggest that an elevated cAMP level alone does not lead to eicosanoid-induced radioprotection of bovine aortic endothelial cell monolayers in vitro. 相似文献
17.
Synthesis of COP (prostaglandins; PG and thromboxanes; Tx) from exogenous and endogenous arachidonic acid (AA) was studied in isolated perfused lungs from rats treated in vivo with a single dose of α-naphthylthiourea (ANTU; 10mg/kg;). Lung dry: wet weight ratios showed changes characteristic of oedema between 6 and 16h after ANTU. Bioassay of COP showed that COP synthesis from exogenous AA was raised above control values in lungs from rats treated with ANTU, reaching a maximum at 16h after treatment. By radioimmunoassay, the major increase was in 6-oxo-PGF1α, with lesser effects on PGE2 and PGF2α levels. Synthesis of bioassayable COP from endogenous AA induced by the calcium ionophore A23187 was increased as early as 2h after ANTU treatment and remained elevated up to 70h. In lungs 28h after ANTU, 6-oxo-PGF1α release was greater than in normal lungs. These results show that in this model of pulmonary oedema, the potential for COP synthesis was increased. From the time course of this effect, increased COP synthesis was probably a response to the initial damage rather than a cause of the oedema. 相似文献
18.
Summary In anaesthetized adult female rats, the renal amino acid handling was measured six days after 5/6 nephrectomy (5/6NX). The distinct rise in blood urea nitrogen as well as the significant reduction in urine flow and GFR indicate an impairment of kidney function. In principle, in 5/6NX rats amino acid plasma concentrations were comparable to those of control animals with two intact kidneys, whereas the fractional excretions (FEAA) of most endogenous amino acids measured were significantly enhanced. After bolus injection of leucine or taurine (each 20 mg/100 g b.wt.) or glutamine (90 mg/ 100 g b.wt.), dissolved in 2m1 normal saline per 100 g b.wt., the FEAA of both the amino acids administered and the endogenous amino acids increased as a sign of overloaded amino acid reabsorption capacity. This effect was more pronounced in 5/6NX rats than in controls. As early as one hour after amino acid load, plasma concentrations and FEAA returned to baseline values of 5/6NX rats. A pretreatment with triiodothyronine (20,µg/100 g b.wt.) or dexamethasone (60 µg/100 g b.wt.), both given intraperitoneally once daily for 3 days, stimulated the renal amino acid transport capacity in 5/6NX rats: the increase in FEAA after amino acid load was significantly lower compared to non-pretreatred animals. This stimulation could be shown for the bolus amino acids and the endogenous amino acids and was more distinct in 5/6NX rats than in controls with two intact kidneys. 相似文献
19.
Shi XZ Lin YM Powell DW Sarna SK 《American journal of physiology. Gastrointestinal and liver physiology》2011,300(1):G99-G108
In gastrointestinal conditions such as bowel obstruction, pseudo-obstruction, and idiopathic megacolon, the lumen of affected bowel segments is distended and its motility function impaired. Our hypothesis is that mechanical stretch of the distended segments alters gene expression of cyclooxygenase-2 (COX-2), which impairs motility function. Partial obstruction was induced with a silicon band in the distal colon of rats for up to 7 days, and wild-type and COX-2 gene-deficient mice for 4 days. Mechanical stretch was mimicked in vitro in colonic circular muscle strips and in primary culture of colonic circular smooth muscle cells (SMC) with a Flexercell system. The rat colonic circular muscle contractility was significantly decreased in the distended segment oral to obstruction, but not in the aboral segment. This change started as early as day 1 and persisted for at least 7 days after obstruction. The expression of COX-2 mRNA and protein increased dramatically also in the oral, but not aboral, segment. The upregulation of COX-2 expression started at 12 h and the effect persisted for 7 days. At 24 h after obstruction, the COX-2 mRNA level in the oral segment increased 26-fold compared with controls. This was not accompanied by any significant increase of myeloperoxidase or inflammatory cytokines. Immunohistochemical studies showed that COX-2 was selectively induced in the colonic SMC. In vitro stretch of colonic muscle strips or cultured SMC drastically induced COX-2 expression. Incubation of circular muscle strips from obstructed segment with COX-2 inhibitor NS-398 restored the contractility. The impairment of muscle contractility in obstructed colon was attenuated in the COX-2 gene-deficient mice. In conclusion, mechanical stretch in obstruction induces marked expression of COX-2 in the colonic SMC, and stretch-induced COX-2 plays a critical role in the suppression of smooth muscle contractility in bowel obstruction. 相似文献
20.
《Prostaglandins, Leukotrienes and Medicine》1984,13(2):211-216
The effect of l-histidine on arachidonic acid metabolism was studied in rabbit splenic fibroblast cultures and human platelets. The noradrenaline-stimulated generation of PGE2 in fibroblast cultures was inhibited by 1-histidine dose dependently. In the same way 1-histidine diminished the aggregation-induced synthesis of TXB2 in human platelets. In contrast to this, after incubation with 1-histidine the generation of PGE2 in activated platelets increased in a dose dependent way up to 240% of pretreatment values. The further increase of 1-histidine concentration resulted in an inhibition of platelet PGE2 synthesis. The present results demonstrate a differential influence of the amino acid l-histidine on cell arachidonic acid metabolism. It is concluded that the supposed anti-rheumatic property of l-histidine is caused by its effect on the synthesis of prostaglandins which are known to be mediators of inflammation. 相似文献