UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main aim of this study was to determine the functional effect of 2-methyl-thio-adenosine diphosphate (2MeS-ADP) on vascular purinoceptors, in comparison with that of a characterised agonist of the P2Y1 receptor, 2-methyl-thio-adenosine triphosphate (2MeS-ATP), and of the P2Y2 receptor, uridine triphosphate (UTP). On phenylephrine-precontracted rat aortic rings, mounted isometrically in organ baths, we found that 2MeS-ADP (10(-9) to 10(-6) M) induced concentration-dependent relaxation of rings with a functional endothelium. Mechanical removal of the endothelium abolished the relaxant effect of 2MeS-ADP. The 2MeS-ADP-induced relaxation of phenylephrine-precontracted rings was inhibited by Nomega-nitro-L-arginine methyl ester (L-NAME) (100 microM) but not by indomethacin (100 microM) or aspirin (1 mM), indicating that the 2MeS-ADP-induced relaxation was nitric oxide (NO) synthase-mediated but not cyclooxygenase-dependent. Repeated stimulation with 2MeS-ADP resulted in desensitisation of the receptor. Under these conditions, the relaxant effect of 2MeS-ATP was abolished. On the contrary, UTP-induced relaxation was not affected, showing that 2MeS-ADP and 2MeS-ATP but not UTP shared the same receptor. Suramin (100 microM), a non-specific P2 inhibitor, abolished the effect of 2MeS-ADP, 2MeS-ATP and UTP. In contrast, pyridoxal-phosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS) and adenosine-3'-phosphate-5'-phosphosulphate (A3P5PS) abolished only the vasodilator responses to 2MeS-ADP and 2MeS-ATP and did not affect the relaxant effect of UTP, showing that 2MeS-ADP acted through the P2Y1 receptor. Clopidogrel, a potent platelet ADP receptor antagonist, at a dose that strongly inhibited ADP-induced platelet aggregation ex vivo, did not modify the relaxant responses to 2MeS-ADP or 2MeS-ATP. In conclusion, these results showed that 2MeS-ADP induces endothelium-dependent, NO-mediated relaxation of rat aortic rings. This effect, resistant to clopidogrel treatment, occurred through activation of the P2Y1 receptor.
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PMID:Relaxant effect of 2-methyl-thio-adenosine diphosphate on rat thoracic aorta: effect of clopidogrel. 1007 99

The objective of this study was to study how the outflow of [3H]purines is altered during a brief period of ischemic-like conditions in superfused hippocampal slices and to show whether it is regulated by P2 purinoceptors and the nitric oxide (NO) pathway. The outflow of [3H]purines increased in response to 5 min of combined hypoxia/hypoglycemia. High performance liquid chromatography analysis verified the efflux of [3H]adenosine-triphosphate, [3H]adenosine-diphosphate, [3H]adenosine-monophosphate, [3H]adenosine, [3H]inosine, and [3H]hypoxanthine in response to ischemic-like conditions. The P2 receptor antagonists suramin and pyridoxal-phosphate-6-azophenyl-2'-4'-disulphonic-acid-tetrasodium (PPADS) reduced significantly the [3H]purine efflux evoked by ischemic-like conditions, showing that P2 purinoceptors are involved in the initiation of purine outflow. The NO synthase inhibitor N-nitro-l-arginine-methyl-ester (l-NAME) attenuated significantly the [3H]purine outflow, evoked by ischemic-like conditions, while 7-nitroindazole (7-NI) caused only a mild decrease in the outflow. The NO donor sodium nitroprusside increased significantly the basal efflux of [3H]purines. In summary, a brief period of combined hypoxia/hypoglycemia induced the efflux of ATP in addition to the outflow of other purines. Since P2 receptor antagonists decreased the [3H]purine outflow evoked by ischemic-like conditions we propose that ATP, acting on P2 purinoceptors, is responsible for further efflux of purines after ischemic-like period. It seems likely that NO is also involved in the regulation of purine outflow, since inhibition of NO production attenuated the [3H]purine outflow, evoked by ischemic-like conditions, while exogenous NO facilitated the basal outflow.
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PMID:Involvement of P2 purinoceptors and the nitric oxide pathway in [3H]purine outflow evoked by short-term hypoxia and hypoglycemia in rat hippocampal slices. 1009 25

In isolated mesenteric arteries of rats, dose-dependent increase in perfusion pressure by adenosine 5'-triphosphate (ATP, 0.1 approximately 3000 nmole) diminished with age. ATP responses of both 4- and 32-week-old rats were enhanced by indomethacin (5 microM), and further by the combination of indomethacin and N(G)-nitro-L-arginine methyl ester (L-NAME, 5 microM). The enhancement with each of the treatments was less in 32-week-old rats than that in 4-week-old rats, and there was no enhancement in 75-week-old rats. The ATP response was enhanced by removing the endothelium only in 4-week-old rats. The constrictions in response to ATP (1000 nmole) in both 4- and 32-week-old rats were equally enhanced by reactive blue 2 (30 micromole) and were inhibited by pyridoxal-phosphate-6-azophenyl-2',4-disulphonic acid (PPADS, 30 microM) and alpha, beta-methylene ATP (alpha, beta-mATP, 100 nmole) to a similar extent. The increased tone which was produced by the perfusion with physiological solution containing 100 mM potassium chloride was greater in older animals. This age-related change in the vascular tone disappeared when the responses were potentiated by L-NAME. These results demonstrate that in rat mesenteric arteries, ATP-induced constriction decreases with age. The age-related decline of vasoconstriction is not likely to arise from the changes in the contractility of smooth muscle, from the counterbalancing regulation by the endothelium, or from the cooperation of P2 purinoceptor subtypes. The density of purinoceptors and some post-receptor signal transduction mechanisms in the vascular smooth muscle cells may change with age. The enhanced ATP response might have special physiological significance in rats during development.
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PMID:Age-related changes in adenosine 5'-triphosphate-induced constriction of isolated, perfused mesenteric arteries of rats. 1022 82

This study examined a possible functional involvement of nitric oxide (NO) in the median eminence (ME) and arcuate nucleus (ARC) after capsaicin treatment in rats. Subcutaneous injection of capsaicin increased nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity in the ARC-ME compared with vehicle treatment. Fos expression was increased in the ARC after capsaicin injection compared with vehicle-treated rats. Pretreatment with the NO synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME) attenuated the effect of capsaicin on Fos expression and NADPH-d reactivity in the ARC-ME in comparison with rats injected with D-NAME, the inactive stereoisomer of L-NAME. These observations suggest that NO makes a major contribution to the response of the ARC-ME to a stressor such as capsaicin.
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PMID:A role for nitric oxide in the median eminence and arcuate nucleus response to capsaicin treatment in rats. 1036 26

Delivery of a normal copy of CFTR cDNA to airway epithelia may provide a novel treatment for cystic fibrosis lung disease. Unfortunately, current vectors are inefficient because of limited binding to the apical surface of airway epithelia. We recently reported that incorporation of adenovirus in a calcium phosphate coprecipitate (Ad:CaPi) improves adenovirus-mediated gene transfer to airway epithelia in vitro and in vivo. To understand better how coprecipitation improves gene transfer, we tested the hypothesis that incorporation in a CaPi coprecipitate increases the binding of adenovirus to the apical surface of differentiated human airway epithelia. When a Cy3-labelled adenovirus was delivered in a coprecipitate, binding increased 54-fold as compared with adenovirus alone. Moreover, infection by Ad:CaPi was independent of fiber knob-CAR and penton base-integrin interactions. After binding to the cell surface, the virus must enter the cell in order to infect. We hypothesized that Ad:CaPi may stimulate fluid phase endocytosis, thereby facilitating entry. However, we found that neither adenovirus nor Ad:CaPi coprecipitates altered fluid phase endocytosis. Nevertheless, Ad:CaPi preferentially infected cells showing endocytosis. Thus, CaPi coprecipitation improves adenovirus-mediated gene transfer by coating the epithelial surface with a layer of virus which enters cells during the normal process of endocytosis.
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PMID:Mechanism by which calcium phosphate coprecipitation enhances adenovirus-mediated gene transfer. 1060 80

Early reports indicated that ECV304 was a spontaneously-transformed line derived from a Japanese human umbilical vein endothelial cells (HUVEC) culture. Many morphological, immunochemical, and genetic studies provided further evidence that ECV304 was a valuable biomedical research tool and could be used to study processes that include angiogenesis in vitro and signal transduction by a variety of G protein-coupled receptors. However, several distinct differences between ECV304 and HUVEC are now apparent and recent reports have indicated genetic similarity between ECV304 and T24/83, a human bladder cancer cell line. To further assess the utility of ECV304 as a human endothelial cell model, we compared the functional responses of ECV304 and T24/83 to a range of G protein-coupled receptor agonists. We also used DNA fingerprinting to karyotype both ECV304 and T24/83. Both ATP and uridine triphosphate (UTP) stimulated inositol phosphate metabolism in ECV304 without alteration of cAMP levels. Comparative data using selective P2Y receptor agonists indicated that this response, leading to calcium mobilization from intracellular stores, was predominantly mediated by the activation of P2Y2 receptors. Similar responses were recorded from both ECV304 and T24/83 cells. ECV304 expressed a relatively high basal activity of NOS that was reduced by L-NAME and stimulated by P2Y2 receptor agonists. In contrast, P2Y2 receptor activation did not induce prostaglandin synthesis in ECV304. Both ECV304 and T24/83 express receptors for adenosine, adrenaline, and calcitonin, which stimulate adenylate cyclase. Proliferation of ECV304 and T24/83 cells, measured by the incorporation of [3H]thymidine into DNA, was largely serum-independent. This was in contrast to parallel experiments with porcine and bovine aortic endothelial cells that indicated a marked serum-dependent increase in DNA synthesis. Genetic analysis confirmed that ECV304 and T24/83 are identical. ECV304 displays some endothelial characteristics and is useful for the study of receptor pharmacology. However, ECV304 is not of HUVEC origin and is therefore an inappropriate cell line to study endothelial cell biology.
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PMID:Critical evaluation of ECV304 as a human endothelial cell model defined by genetic analysis and functional responses: a comparison with the human bladder cancer derived epithelial cell line T24/83. 1065 1

Nitric oxide (NO) may subserve different functions in different central neurons subjected to axotomy. The difference may depend on whether the neurons basally express neuronal nitric oxide synthase (nNOS), a biosynthetic enzyme of NO. This is supported by our previous finding that suggests the differential role of NO in neurons of nucleus dorsalis (ND) and red nucleus (RN) which have different basal expression of nNOS. This study aimed to establish firmly the functions of NO, as revealed by nNOS immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry, by the administration of endogenous NO donor, l-arginine (l-arg), and NOS inhibitor, l-N(G)-nitroarginine methyl ester (l-NAME). To relate the role of NO to glutamate receptors (GluR), the distributions of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-d-aspartate receptor (NMDAR) in the two nuclei were revealed by immunohistochemical techniques. nNOS immunoreactivity was void in ND neurons, but expressed weakly in the RN normally. It was induced in ipsilateral ND neurons and upregulated on both sides of RN after spinal cord hemisection. Neuronal loss in the ipsilateral ND was augmented by l-arg, but reduced by l-NAME. In the contralateral RN, l-arg attenuated neuronal loss. NMDAR1 was present in most neurons in ND. After axotomy, some NMDAR1 immunoreactive neurons of the ipsilateral ND were induced to express NOS, whereas RN neurons showed strong staining for NMDAR1 and all the AMPA subunits. Most of the NOS-positive neurons in the RN were coexistent with GluR2 in normal rats and those subjected to axotomy. The present data demonstrated that NO exerted neurodestructive function in the non-NOS-containing ND neurons characterized by NMDAR as the predominant glutamate receptor. NO might be beneficial to the NOS-containing RN neurons. This could be attributed to the presence of GluR2. Possible diverse synthesizing pathways of NO in two different central nuclei were suggested from the observation that NOS was colocalized with NADPH-d in ND neurons, but not in RN neurons.
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PMID:Neuroprotective and neurodestructive functions of nitric oxide after spinal cord hemisection. 1068 69

Nitric oxide (NO) is one of the important regulators of cardiac metabolism and function as well as of tissue perfusion. Myocardial NO formation is increased during ischemia and reperfusion. We investigated the roles of endogenous NO in myocardial metabolism during ischemia and reperfusion independent of tissue perfusion changes. In an open-chest pig model, a bolus infusion of 20 mg/kg of N(G)-nitro l -arginine methyl ester (l -NAME), a NO synthase inhibitor, did not alter the regional myocardial perfusion compared with a control saline injection, as measured by colored microsphares. Using(31)P-nuclear magnetic resonance spectroscopy, we showed that the tissue levels of pH and adenosine triphosphate (ATP) but not those of creatine phosphate were significantly preserved in the l -NAME group compared with the placebo group during the subsequent 15-min regional ischemia. Thus, l -NAME reduced myocardial ATP utilization during ischemia, and the mechanism underlying these effects is independent of tissue perfusion changes. However, l -NAME did not accelerate the recovery of ATP levels following reperfusion, suggesting distinct roles of endogenous NO during reperfusion.
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PMID:Nitric oxide inhibition improved myocardial metabolism independent of tissue perfusion during ischemia but not during reperfusion. 1073 37

Although capsaicin has been shown to activate certain neuronal groups in the hypothalamus and amygdala, the neurotransmitters involved and the exact mechanism of action are not clearly understood at present. The aim of this study was to examine the hypothesis that the effect of capsaicin in the rat hypothalamus and amygdala primarily involves direct activation of the endogenous nitric oxide synthase (NOS) neurons responsible for the synthesis of nitric oxide (NO). Subcutaneous capsaicin injection in male rats, compared with vehicle, caused a significant increase in Fos expression in the paraventricular nucleus (PVN), supraoptic nucleus (SON), and medial and cortical amygdala. The expression of nicotinamide adenine dinucleotide phosphate diaphorase, a histochemical marker for NOS, was also increased in these brain areas in addition to the periventricular and lateral hypothalamic area and central amygdaloid nucleus. Also, capsaicin significantly increased the expression of neuronal NOS messenger RNA and protein in the PVN, SON, and medial amygdala as demonstrated by in situ hybridization and immunohistochemistry, respectively. A higher proportion of the NOS neurons in the PVN, periventricular region, SON and amygdala showed Fos expression in response to capsaicin than vehicle injection. There was little, if any, Fos activation in the NOS-positive neurons in the lateral hypothalamic area. The capsaicin-induced activation of the hypothalamic PVN and SON neurons and the medial amygdaloid nucleus was attenuated in the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) -pretreated animals in comparison with the inactive enantiomer D-NAME. These observations indicate that activation of the endogenous NOS system and production of NO constitute a major pathway through which capsaicin exerts its effect within the hypothalamus and amygdala.
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PMID:Importance of endogenous nitric oxide synthase in the rat hypothalamus and amygdala in mediating the response to capsaicin. 1088 Sep 96

The kinin B1 receptor is an inducible receptor expressed in response to inflammatory mediators. We sought to determine whether kinin B1 receptor can be expressed on human brain endothelial cells (HBECs) in vitro and whether signaling via this receptor can regulate permeability and chemokine production properties of these cells. Multiplex RT-PCR amplification and western blot techniques were used to evaluate B1 receptor expression by HBECs. Although B1 receptor mRNA and protein could not be detected on resting HBECs, interferon-gamma induced a dose- and time-dependent up-regulation of B1 receptor mRNA and protein on HBECs. Stimulation of interferon-gamma-treated HBECs with the selective B1 agonist R-838 (Sar [D-Phe8] des Arg9-BK) induced a dose- and time-dependent increase in the production of inositol 3,4,5 tri-phosphate and nitric oxide. Permeability of the HBECs monolayer, as measured by BSA diffusion, was significantly increased by application of the B1 agonist. This biological effect of R-838 could be prevented by R-715, a B1 receptor antagonist and by L-NAME, a nitric oxide synthase blocker. R-838 also inhibited interleukin-8 release from HBECs. We demonstrate that B1 receptors can be up regulated on the surface of HBECs by molecules released during inflammatory response and that signaling via this receptor can regulate BBB permeability and chemokine production in vitro.
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PMID:Kinin B1 receptor expression and function on human brain endothelial cells. 1107 80

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