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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although neuroanatomical and neurophysiological features of neurons in the ferret trachea have been studied, the neural mediators associated with this plexus have not been completely characterized. The purpose of this study was to examine the occurrence of choline acetyltransferase (ChAT), nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), and substance P(SP) in the intrinsic neurons of this plexus. The distribution of double- and triple-labeled neurons was quantified in cryostat sections and in whole mounted specimens to evaluate the neurochemical profiles. About 85% of the nerve cell bodies with ChAT immunoreactivity (ChAT-IR) were located in ganglia of the longitudinal trunks or the closely associated bridge ganglia. Approximately 15% of ChAT-positive neurons were in ganglia of the superficial muscular plexus. Conversely, VIP-IR neurons were most frequent in the superficial muscular plexus (>75%) and, <10% were observed in the longitudinal trunks or bridge neurons. Most NOS- and SP-IR neurons were also located in the superficial muscular plexus. The following distribution of neurochemical profiles was determined for neurons of the superficial muscular plexus: 11% only NOS, 20% only VIP, 5% only SP, 67% NOS and VIP, and 40% VIP and SP. NOS, VIP, and SP were frequently localized in the same nerve cell body. The occurrence of nerve terminals containing only SP located around the borders of individual NOS/VIP/SP-containing neurons suggests possible sensory innervation to the airway neurons. The results demonstrate that: (1) most cholinergic nerves do not contain VIP, NOS, or SP; (2) cholinergic neurons are predominantly located in the longitudinal trunk ganglia; (3) VIP, NOS, and SP are predominantly located in the superficial muscular plexus ganglia; and (4) nerve terminals containing exclusively SP, suggesting possible sensory origin, are closely associated with some neurons in the plexus.
Am J Respir Cell Mol Biol 1996 Mar
PMID:Neurochemical characterization of intrinsic neurons in ferret tracheal plexus. 884 70

Nitric oxide (NO) plays a modulatory role on cell growth and differentiation, biological processes that occur under the control of various signal transduction mechanisms, including those triggered by activation of membrane receptors for polypeptide growth factors. The increases in intracellular Ca2+ concentration elicited by the activation of these receptors are sustained by release of the cation from intracellular stores and by stimulation of this influx from the extracellular medium. Using NIH 3T3 cells overexpressing the human epidermal growth factor receptor, we investigated both of these processes stimulated by the administration of epidermal and platelet-derived growth factors as the receptor agonists. Pharmacological and functional analyses carried out on Fura-2-loaded cells showed that Ca2+ influx elicited by both growth factors is the summation of two distinct pathways, with the major pathway dependent on and the minor pathway independent of store depletion. Exposure of the cells to either No donors or NO synthase inhibitors induced increase and inhibition, respectively, of the two components of Ca2+ influx. When Ca2+ release was investigated, the above drugs were also active but in the opposite direction. The effects of NO were mimicked by the cGMP analogue 8-Br-cGMP and abolished by two cGMP-dependent protein kinase I inhibitors, whereas the cAMP analogue 8-Br-cAMP and two protein kinase A inhibitors had no appreciable effects. In addition, growth factors induced an increase in cGMP formation, an effect that was prevented by NO synthase inhibitors. In conclusion, NO appears to exert a feedback modulatory control on CA2+ responses to growth factor administration. Such a control might contribute to the inhibitory effect of NO on growth previously reported with various cell types.
Mol Pharmacol 1995 Dec
PMID:Growth factor-induced Ca2+ responses are differentially modulated by nitric oxide via activation of a cyclic GMP-dependent pathway. 884 7

Acemannan is a polydispersed beta-(1,4)-linked acetylated mannan with antiviral properties. It is an immunomodulator, and studies in our laboratory have shown that it causes activation of macrophages. Inducible NO synthase is generally expressed after transcriptional induction and is known to mediate some of the cytotoxic action of activated macrophages. Acemannan, in the presence of interferon-gamma, greatly increased the synthesis of NO in RAW 264.7 cells. This increase was preceded by increased expression of mRNA for the inducible form of macrophage NO synthase. Preincubation with pyrrolidine dithiocarbamate inhibited the induction, indicating the involvement of nuclear factor-kappa B. These results suggest that acemannan causes the activation of macrophages by increasing the level of NO synthase at the level of transcription.
Mol Pharmacol 1996 Oct
PMID:Acemannan, a beta-(1,4)-acetylated mannan, induces nitric oxide production in macrophage cell line RAW 264.7. 886 33

Nitric oxide (NO) is a signalling molecule that is produced by mesangial cells and renal tubular epithelial (RTE) cells. It plays a role in the regulation of glomerular and tubular function. In renal cells, NO is synthesized by the inducible isoform of the enzyme nitric oxide synthase (NOS). Thyroid hormone modulates the activity of neuronal NOS; therefore, we examined whether triiodothyronine (T3) stimulated the activity of inducible iNOS in mesangial cells, LLC-PK1 cells (analogue of the proximal tubule) and MDCK cells (analogue of the distal tubule). T3 (concentration range: 10(-10)-10(-7) M) had no effect on NO synthesis or iNOS protein expression by the three renal cell types. In addition, T3 did not modulate NO production in RAW 264.7 cells, a murine macrophage cell line, confirming that the hormone had no effect on iNOS activity. We conclude that, unlike its effect on neuronal NOS, T3 does not regulate iNOS activity in mesangial cells, RTE cells, or macrophages, and that the effects of T3 on renal cell growth and function are not mediated by inducible increases in NO synthesis.
Res Commun Mol Pathol Pharmacol 1996 Jul
PMID:Effect of triiodothyronine on nitric oxide production in mesangial cells and renal tubular epithelial cells. 886 71

Glutamate (Glu) uptake is the primary mechanism for its removal from the synapse. In genetic audiogenic seizures (AGS), Glu uptake is elevated prior to the appearance of seizures. Increased Glu uptake is also observed in synaptosomes from normal mice preincubated with lithium or nitroarginine, an NO synthase inhibitor. Pertussis and cholera toxins cause a marked reduction in Glu uptake. In contrast, neither lithium nor nitroarginine affected Glu uptake by synaptosomes from genetic epileptic mice. Arachidonic acid inhibits Glu uptake, whereas synaptosomes from epileptic mouse brain appear to be more sensitive to arachidonic acid as indicated by a shift of the inhibition curve to the left. These observations are indicative of the possible regulation of Glu uptake by second messengers and its alteration in genetic epilepsy.
Mol Chem Neuropathol
PMID:Possible regulation of high-affinity glutamate uptake in synaptosomes of normal and epileptic mice. 887 51

Since the discovery that nitric oxide is an endogenous vasodilator responsible for endothelium-derived relaxing factor activity, nitric oxide has been found in many different cell types and implicated in many diverse biological processes. Because pharmacological blockade does not distinguish between the three major isoforms of nitric oxide synthase, the tissue and enzyme source of nitric oxide is unclear in many situations. Targeted disruption of the genes for the various isoforms of nitric oxide synthase offers a useful genetic approach to study the roles of each isoform and to examine the effects of their deletion on physiological processes in intact animals. Here we review the phenotypes of the various nitric oxide synthase mutant mice and examine what they reveal about the complexities of the nitric oxide signaling system and about molecular and physiological compensations brought into play in the absence of individual isoforms.
J Mol Med (Berl) 1996 Aug
PMID:Genetic analysis of nitric oxide synthase isoforms: targeted mutation in mice. 887 55

In patients with septic shock or inflammatory cardiac diseases like myocarditis myocardial contractility is depressed. These patients have elevated circulating levels of bacterial endotoxins (lipopolysaccharides, LPS) and pro-inflammatory cytokines like interleukin-1 beta (IL-alpha 1 beta) or tumor necrosis factor-alpha (TNF-alpha). It is not clear, whether LPS and/or cytokines have direct inotropic effects on cardiomyocytes and whether these effects are mediated via the L-arginine-nitric oxide synthase (NOS) pathway as demonstrated in vascular smooth muscle cells. Therefore, we examined the direct effects of LPS. IL-1 beta and TNF-alpha on contractility and cGMP content in isolated guinea-pig ventricular cardiomyocytes. Furthermore, the influence of the NOS inhibitor NG-nitro-L-arginine (L-NNA) and dexamethasone on these effects was studied as well as inducible NOS (iNOS) protein expression. LPS (1000 ng/ml), IL-1 beta (25 ng/ml) and TNF-alpha (100 ng/ml) decreased contractility by 48%, 55% and 65% and augmented cGMP content by 135%, 88% or 70% after long-term treatment (18 h) in cardiomyocytes, without altering contractility or cGMP content after short-term treatment (30 min). These effects were blocked by L-NNA (100 microM) and dexamethasone (3 microM). Furthermore iNOS protein was expressed in LPS- and cytokine-treated cardiomyocytes. These findings demonstrate that LPS. IL-1 beta and TNF-alpha have direct negative inotropic effects on cardiomyocytes, which are accompanied by an increase in cGMP content. These effects are mediated via de novo synthesis of a myocardial iNOS. The direct negative inotropic effects of endotoxins and cytokines on cardiomyocytes may in part contribute to the contractile dysfunction observed in patients with septic shock or inflammatory cardiac diseases.
J Mol Cell Cardiol 1996 Aug
PMID:Endotoxin and cytokines induce direct cardiodepressive effects in mammalian cardiomyocytes via induction of nitric oxide synthase. 887 73

Patients with systemic hypertension of various etiologies maintain their pulmonary artery pressures within normal limits. We have reported in isolated perfused rat lungs that low basal tone appears to be regulated by nitric oxide (NO)-dependent and -independent mechanisms of soluble guanylate cyclase activation, and similar results are seen in isolated small pulmonary arteries (PA) from these animals. The abdominal aorta of rats was ligated above the left and below the right renal artery (aortic coarctation, AC). The mean arterial pressure (MAP) and pulmonary artery pressure (PAP) of 24-h post-AC rats (MAP 123 +/- 7.1 mm Hg and PAP 4.2 +/- 0.9 mm Hg) showed no significant change when compared with those of sham control rats (MAP 116 +/- 7.0 mm Hg and PAP 5.0 +/- 0.04 mm Hg). Hypoxic contractions in isolated small rat PA (160 to 260 microns diameter) were significantly increased from 56.7 +/- 12.0 mg in the control group to 139 +/- 31 mg in the 24-h post-AC rats (P < 0.05). PA contractions in the presence of 100 microM nitro-L-arginine (NLA) increased from 102 +/- 34 mg among the sham control group to 261 +/- 30 mg among the 24-h post AC rats (P < 0.05). After NLA, the hypoxic contractions decreased to 15 +/- 2.9 mg in the control rats and 45 +/- 16 mg in the 24-h post-AC rats when compared with pre-NLA values (P < 0.05). Western and Northern blotting of protein and messenger ribonucleic acid (mRNA) extracted from the whole rat lung showed a significant rise in endothelial cell nitric oxide synthase (EcNOS; 207 +/- 34%) and EcNOS mRNA (2-fold) when comparing controls with 24-h post-AC rats. These data indicate that there is increased EcNOS activity and synthesis that maintain low PA tone in these rat models as early as 24 h after AC; in addition, this effect is independent of the systemic blood pressure.
Am J Respir Cell Mol Biol 1996 Oct
PMID:Early regulatory changes in rat pulmonary artery of renin-dependent systemic hypertension models. 887 80

1. The expression of neuronal isoform of nitric oxide synthase (nNOS) was studied in human retinal tissues. The cDNA sequence was cloned in human retinal poly (A)+ RNA by the RT-PCR method and encompassed an open-reading frame of 4,302 bp encoding 1,434 amino acids. This sequence showed a possibility of genetic polymorphism in comparison to human brain form. 2. Restriction fragment length polymorphism (RFLP) patterns of a partial cDNA fragment suggest that there is genetic polymorphism in the neuronal form of NOS. Important differences were observed in a certain region between human retinal and brain froms. This region is a result of frame shift by the addition of three cytidines. In this study, regions from human brain (cerebellum) and skeletal muscle as well as retina were sequenced to confirm the difference in this region. The sequences from these tissues were completely identical. This indicated that genetic polymorphism of nNOS gene was due to single base substitution and not frame shift phenomenon by addition or deletion of bases. 3. The nNOS mRNA of approximately 12 kb was detected by northern blot analysis. The lower level of the expression was distinguished in comparison to those of human brain and skeletal muscle. The cDNA transiently transfected into CHO-K1 cells expressed a protein which contained a significant level of NOS activity. The size of the nNOS was found to be approximately 160 kDa by both in vitro and in vivo translation systems. This NOS was calcium dependent and the K(m) for arginine was 4.4 microM. 4. The Ca+2, L-arginine and NADPH dependency along with the inhibitory effect of N-nitro-L-arginine on NOS activity were evaluated. The finding of a constitutive from of NOS in human retina, which is calcium-NADPH dependent, gives further credence to the possible role of nitric oxide in retinal function and neuronal diseases.
Cell Mol Neurobiol 1996 Aug
PMID:Neuronal isoform of nitric oxide synthase is expressed at low levels in human retina. 887 52

Neuronal nitric oxide synthase (nNOS) mRNA levels and NADPH diaphorase (NADPH-d) staining were compared in the frontal cortex, visual cortex and hippocampus (dentate gyrus and CA subfields of Ammon's horn) of five Alzheimer's disease (AD) and six control brains. The cellular abundance of nNOS mRNA was quantified by in-situ hybridisation using 35S-labelled antisense oligonucleotides complementary to the human nNOS sequence. Although the mean level of nNOS expression was decreased in all three regions in AD cases as compared to controls, it did not reach significance. Neurones positively labelled for nNOS mRNA and neurones positive for NADPH-d histochemistry displayed similar distribution in control and AD cases. In AD brains the density of neurones having detectable levels of nNOS mRNA was significantly decreased in the white matter underlying the frontal cortex (P < 0.05) but not in the frontal cortex gray matter; no change was observed in the gray or white matter of the visual cortex in AD. The number of cells expressing detectable levels of nNOS mRNA in the hippocampus was also significantly decreased (P < 0.05) in AD. The density of NADPH-d-positive cells was not significantly decreased in the gray or white matter of the frontal or visual cortices in AD compared to controls; however, the number of NADPH-d-positive cells was significantly decreased in the hippocampus (P < 0.01). These data indicate that although the cellular abundance of nNOS mRNA is not significantly decreased in these three regions in AD, there is a significant decrease in the number of cells expressing detectable levels of nNOS mRNA in the white matter underlying the frontal cortex and in the dentate gyrus and CA subfields of the hippocampus in AD. Furthermore, there was also a significant decrease in the number of NADPH-d-positive cells in the dentate gyrus and CA subfields of the hippocampus in AD as compared to controls. These results suggest specific populations of nNOS/NADPH-d cells in the white matter underlying the frontal cortex and in the hippocampus are vulnerable in AD. The implications of these findings are discussed.
Brain Res Mol Brain Res 1996 Sep 05
PMID:Neuronal nitric oxide synthase (nNOS) mRNA expression and NADPH-diaphorase staining in the frontal cortex, visual cortex and hippocampus of control and Alzheimer's disease brains. 888 32


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