Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuronal degeneration that occurs in both ischemia and degenerative neurologic illnesses may involve excitotoxic mechanisms. In the present study, we examined whether cortical lesions with agonists acting at subtypes of glutamate receptors result in selective patterns of neuronal death. Injections of quinolinic acid, NMDA, homocysteic acid, kainic acid (KA), and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) were made at 2 sites in the dorsolateral frontoparietal cortex in rats. After 1 week, the cerebral cortex was either dissected for neurochemical studies, or animals were perfused for histologic evaluation. Concentrations of somatostatin (SS), neuropeptide Y (NPY), substance P (SP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay, while amino acids and catecholamines were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. NMDA agonists (quinolinic acid, homocysteic acid, and NMDA itself) resulted in dose-dependent reductions in glutamate and GABA, while SS, NPY, SP, CCK, and VIP were either unchanged or significantly increased in concentration. KA and AMPA at doses that resulted in comparable GABA depletions caused significant reductions in SS concentrations. Markers of cortical afferents were spared. All excitotoxins resulted in dose-dependent marked increases in uric acid concentrations. Histologic examination verified that lesions with NMDA agonists produced relative sparing of NADPH-diaphorase, SS, VIP, and CCK neurons. These results show that NMDA excitotoxin lesions result in a pattern of selective neuronal damage in the cerebral cortex that is similar to that which occurs in both ischemia and Huntington's disease.
 ...
PMID:Neurochemical characterization of excitotoxin lesions in the cerebral cortex. 167 Jul 82

The distribution of nitric oxide producing neurones in the medulla oblongata of the cat was investigated using nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry, and nitric oxide synthase (NOS) immunohistochemistry. The pattern of staining obtained with both methods was found to be similar. Strongly diaphorase and NOS reactive neurones were present in the paramedian and lateral tegmental fields, including the regions occupied by the A1/C1 catecholamine cell groups, the nucleus ambiguus and lateral reticular nucleus, and in a number of sensory nuclei including the nucleus of the tractus solitarius and the dorsal column nuclei. The extent of co-localization of NADPH-diaphorase with a number of neuropeptides and neurotransmitters was investigated by combining NADPH-diaphorase histochemistry with immunocytochemistry for neuropeptide Y, somatostatin, glutamate, cholecystokinin and tyrosine hydroxylase. NADPH-diaphorase reaction product was observed in neurones immunoreactive for glutamate and somatostatin. These double-labelled cells were found in the paramedian region, lateral reticular field, the nucleus prepositus hypoglossi and in the rostral nucleus of the tractus solitarius. In the rostral ventrolateral medulla NADPH-diaphorase/somatostatin immunoreactive cells were found in the paragigantocellular nucleus. NADPH-diaphorase/glutamate immunoreactive cells overlapped the nucleus ambiguus, the lateral reticular nucleus and the A1/C1 catecholaminergic cell groups. In addition, a few NADPH-diaphorase/glutamate immunoreactive cells were found in the paraolivary area and gigantocellular tegmental field, in the external cuneate and infratrigeminal nuclei. The functional implications of the co-localization of nitric oxide with these neurotransmitters in areas of the medulla concerned with cardiovascular regulation is discussed.
 ...
PMID:Co-localization of neurotransmitter immunoreactivities in putative nitric oxide synthesizing neurones of the cat brain stem. 754 Dec 9

Nitric oxide (NO) plays an important physiological role in regulating gastrointestinal motility. Involvement of endogenous NO was evaluated in the response to non-adrenergic, non-cholinergic (NANC) nerve stimulation of the dog sphincter muscle of Oddi. Transmural electrical stimulation (TES), nicotine (10(-5) M) and K+ (10 mM) produced only a relaxation in the sphincter muscle strips contracted with substance P, which was not potentiated by atropine. The TES-induced relaxation was abolished by tetrodotoxin (3 x 10(-7) M) and oxyhaemoglobin (1.6 x 10(-5) M), but not affected by atropine (10(-7) M), propranolol (10(-7) M), phentolamine (10(-7) M), indomethacin (10(-6) M), cholecystokinin (CCK, 10(-8) M) and vasoactive intestinal polypeptide (VIP, 10(-8) M). The relaxation was also abolished by treatment with NG-nitro-L-arginine (L-NA, 10(-5) M), an NO synthase inhibitor. Nicotine produced a transient relaxation, which was abolished by tetrodotoxin, hexamethonium (10(-5) M) and L-NA, but not affected by atropine and NG-nitro-D-arginine (D-NA, 10(-5) M). The addition of K+ elicited a transient relaxation, which was abolished by tetrodotoxin and L-NA. The inhibitory effects of L-NA were antagonized by L-arginine (10(-3) M). The presence of neurons containing nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase was histochemically demonstrated in the sphincter of Oddi. These findings may indicate that TES, nicotine and K+ liberate NO from NANC inhibitory nerve which is involved in the relaxation of the dog sphincter of Oddi. The muscular tone does not seem to be regulated by cholinergic nerves under the experimental conditions used.
 ...
PMID:Functional role and histological demonstration of nitric-oxide-mediated inhibitory nerves in dog sphincter of Oddi. 857 10

Neurons in the human adrenal medulla, stained by the NADH-diaphorase reaction, were counted and their neurochemical markers were investigated by double labeling immunofluorescence with special reference to substance P. The findings indicate a significant participation of intramedullary nerve cell bodies in human adrenal innervation with 40.4 neurons/mm3 adrenal medulla. Substance P-immunoreactive neurons, which made up approximately 20% of all neurons, exhibited heterogeneity by co-localization of immunoreactivities for dynorphin, for cholecystokinin, and for neurofilament triplet. Substance-P-immunolabeled neurons were always nonreactive for calcitonin gene-related peptide, for vasoactive intestinal polypeptide, or for tyrosine hydroxylase, the rate-limiting enzyme of catecholamine synthesis. These chemical phenotypes of intramedullary neurons reveal immunohistochemical similarities with postganglionic neurons in parasympathetic ganglia or with enteric neurons, suggesting a hitherto unrecognized functional significance of the intrinsic nervous system in the human adrenal gland.
 ...
PMID:Immunohistochemical heterogeneity of nerve cells in the human adrenal gland with special reference to substance P. 860 96

In this study we evaluated the role of nitric oxide (NO) on gallbladder motility in the normal prairie dog by 1) immunohistochemistry, 2) an enzymatic assay for NO synthase (NOS), and 3) an in vivo model to measure whole gallbladder tone and contractility. NOS was localized to gallbladder mucosal cells by NADPH-diaphorase and polyclonal antibodies to a constitutive brain NOS. Gallbladder mucosal homogenates demonstrated total NOS activity in the range of 578 +/- 115 pmol x mg protein(-1) x 30 min(-1). Blockade of NOS activity in vivo using N(omega)-nitro-L-arginine methyl ester resulted in an up to 80% increase in gallbladder tone from basal. A 40% increase in tone was seen with methylene blue, suggesting that tone was maintained by both NO activation of guanylate cyclase and possibly direct effects on Ca2+ channels. An exogenous nitrosothiol, S-nitroso-N-acetyl-cysteine, abolished cholecystokinin (CCK) octapeptide and bethanechol-stimulated gallbladder contraction. We conclude that the prairie dog gallbladder contains constitutive NOS and synthesizes NO, which is important for the maintenance of basal gallbladder tone and is an inhibitor of the contractile response of the gallbladder to agonists such as CCK and bethanechol.
 ...
PMID:Nitric oxide and gallbladder motility in prairie dogs. 914 7

The muscle and epithelial tissues of the gallbladder are regulated by a ganglionated plexus that lies within the wall of the organ. Although these ganglia are derived from the same set of precursor neural crest cells that colonize the gut, they exhibit structural, neurochemical and physiological characteristics that are distinct from the myenteric and submucous plexuses of the enteric nervous system. Structurally, the ganglionated plexus of the guinea pig gallbladder is comprised of small clusters of neurons that are located in the outer wall of the organ, between the serosa and underlying smooth muscle. The ganglia are encapsulated by a shell of fibroblasts and a basal lamina, and are devoid of collagen. Gallbladder neurons are rather simple in structure, consisting of a soma, a few short dendritic processes and one or two long axons. Results reported here indicate that all gallbladder neurons are probably cholinergic since they all express immunoreactivity for choline acetyltransferase. The majority of these neurons also express substance P, neuropeptide Y, and somatostatin, and a small remaining population of neurons express vasoactive intestinal peptide (VIP) immunoreactivity and NADPH-diaphorase enzymatic activity. We report here that NADPH-diaphorase activity, nitric oxide synthase immunoreactivity, and VIP immunoreactivity are expressed by the same neurons in the gallbladder. Physiological studies indicate that the ganglia of the gallbladder are the site of action of the following neurohumoral inputs: 1) all neurons receive nicotinic input from vagal preganglionic fibers; 2) norepinephrine released from sympathetic postganglionic fibers acts presynaptically on vagal terminals within gallbladder ganglia to decrease the release of acetylcholine from vagal terminals; 3) substance P and calcitonin gene-related peptide, which are co-expressed in sensory fibers, cause prolonged depolarizations of gallbladder neurons that resemble slow EPSPs; and 4) cholecystokinin (CCK) acts presynaptically within gallbladder ganglia to increase the release of acetylcholine from vagal terminals. Results reported here indicate that hormonal CCK can readily access gallbladder ganglia, since there is no evidence for a blood-ganglionic barrier in the gallbladder. Taken together, these results indicate that gallbladder ganglia are not simple relay stations, but rather sites of complex modulatory interactions that ultimately influence the functions of muscle and epithelial cells in the organ.
 ...
PMID:Innervation of the gallbladder: structure, neurochemical coding, and physiological properties of guinea pig gallbladder ganglia. 932 15

Ischemic brain injury in neonates can result in the degeneration of cortical and subcortical areas of brain and is associated with neurologic deficits. One approach to restoring function in conditions of ischemic brain injury is the use of neural transplants to repair damaged connections. This approach has been shown to reestablish neural circuitry and to ameliorate associated motor deficits in models of neonatal sensorimotor cortex damage. In this study, we utilized the Rice et al. rodent model of neonatal ischemic-hypoxic (IH) brain injury to assess whether transplantation of fetal neocortical tissue can promote functional recovery in tests of sensorimotor and locomotor ability throughout development and as adults. We show that animals that received neocortical grafts 3 days following the IH injury performed significantly better as adults on two measures of motor ability, the Rota-Rod treadmill and apomorphine-induced rotations, than did control animals that received sham transplants after the IH injury. Transplants were identifiable in 72% of the animals 10-12 weeks after implantation. Histochemical studies revealed that while the transplanted tissue did not establish normal cortical cytoarchitecture, cells and fibers within the grafts stained for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), choline acetyl transferase (ChAT), cholecystokinin (CCK), and glial fibrillary acidic protein (GFAP). These results suggest that transplantation of fetal neocortical tissue following IH injury in the neonatal period is associated with amelioration of motor deficits and that the grafted tissue demonstrated a neurochemical phenotype that resembled normal neocortex. This approach warrants continued investigation in light of potential therapeutic uses.
 ...
PMID:Transplantation of fetal neocortex ameliorates sensorimotor and locomotor deficits following neonatal ischemic-hypoxic brain injury in rats. 934 72

Cholecystokinin octapeptide (CCK), acetylcholine (ACh) and ceruletide have been shown to produce contraction in bullfrog (Rana catesbeiana) gallbladder strips. Agents capable of relaxing the bullfrog gallbladder are less numerous. Calcitonin gene-related peptide reduced the amount of both CCK- and ACh-induced tension in bullfrog gallbladder strips. The purpose of this study was to determine whether vasoactive intestinal peptide (VIP), nitric oxide (NO) and the second messengers cyclic GMP or cyclic AMP had any effect on gallbladder motility in the bullfrog. In vitro tension studies using l-NG-nitro-arginine methyl ester, Methylene Blue, sodium nitroprusside and N2,2'-O-dibutyryl guanosine 3',5'-cyclic monophosphate suggested that nitric oxide did not modulate gallbladder motility in the bullfrog gallbladder. Histochemical staining for NADPH diaphorase (nitric oxide synthase) failed to demonstrate nerve fibers containing nitric oxide synthase in the bullfrog gallbladder. In vitro studies demonstrated that VIP had no effect on CCK-induced tension. However, in vitro studies using either 8-bromoadenosine 3',5'-cyclic monophosphate or forskolin demonstrated that both agents relaxed strips precontracted with CCK. The results of this study suggested that, while neither NO nor VIP had a role in modulating bullfrog gallbladder motility, cyclic AMP was capable of modulating bullfrog gallbladder motility.
 ...
PMID:Cyclic AMP induces a relaxation response in the bullfrog Rana catesbeiana, but nitric oxide does not. 935 74

The aim of the present study was to analyze the neurochemical properties of the centrifugal visual system (CVS) of the quail using an immunohistochemical approach by testing 16 neuropeptides (angiotensin: ANG, bradykinin: BK, cholecystokinin, dynorphin, L and M-enkephalin, beta-endorphin: beta-END, galanin, alpha-neoendorphin, neurokinin A, neuropeptide Y (NPY), ocytocin, somatostatin, substance P, vasopressin, vasoactive intestinal polypeptide) and three neurotransmitters or their synthetic enzymes (choline acetyltransferase: ChAT, tyrosine hydroxylase: TH, serotonin: 5-HT and nitric oxide synthase: NOS, including the histochemical nicotinamide adenine dinucleotide phosphate diaphorase technique). For each substance, the somatic and afferent fiber and terminal labeling was analyzed within the nucleus isthmo-opticus (NIO) and the ectopic area (EA) and compared with that of retinopetal cell bodies labeled retrogradely with RITC following its intraocular injection (double-labeling procedure). The results showed that none of the centrifugal neurons were reactive to any of the substances tested. In contrast, all with the exception of ANG, BK and beta-END, labeled fibers and terminals within the EA and only four (ChAT, 5-HT, NPY and NOS) within the NIO. Possible sources of these immunoreactive fibers terminating in the NIO and EA were investigated by mapping the somatic immunolabeling of the different substances within brainstem regions previously shown by Miceli and other authors to project upon the centrifugal neurons. The data suggests that, besides the rapid retino-tecto-NIO-retinal loop, which facilitates the transfer of meaningful or more relevant information within particular portions of the visual field, the multiple afferent input which stems from various brainstem regions utilizes a wide range of neuroactive substances. Some of these afferent projections upon the centrifugal neurons appear to belong to nonspecific systems which might play a role in modulating the excitability of centrifugal neurons as a function of arousal.
 ...
PMID:An immunohistochemical study of putative neuromodulators and transmitters in the centrifugal visual system of the quail (Coturnix japonica). 971 61

Generalized tonic-clonic seizures of brain stem origin in rats are associated with acute induction of neuronal Fos in several discrete regions of the brain. One particular site in the dorsal pons shows remarkable Fos induction following generalized tonic seizures induced by maximal electroshock in normal rats or by audiogenic stimulation in genetically epilepsy-prone rats (GEPRs). Although this area shows the most intense Fos induction of any brain area following generalized tonic seizures, its identity has been uncertain. Based on its general location, we hypothesized that this nucleus was either 1) a component of the pedunculopontine tegmentum nucleus-pars compacta (PPTn-pc) or 2) the superior lateral subnucleus of lateral parabrachial area (LPBsl). The present study used Fos-protein immunocytochemistry in combination with the reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry, cholecystokinin (CCK) immunocytochemistry, and neuronal tract-tracing to determine the identity of this cluster of Fos-immunoreactive neurons in the dorsal pons. Following maximal electroshock seizure (MES), Fos labeling was compared to NADPH diaphorase staining (a marker for cholinergic neurons of the PPTn-pc); retrograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected into the ventromedial nucleus of the hypothalamus (VMH; to identify the LPBsl) or CCK immunoreactivity (also a marker for LPBsl neurons). Results showed this cluster of Fos immunoreactive (FI) neurons to be closely associated, but not overlapping, with the lateral and most caudal aspect of the PPTn-pc. Alternatively, WGA-HRP retrograde-labeled neurons corresponded precisely with the seizure-induced FI neurons. Additionally, the location of CCK immunoreactive neurons directly overlapped with the FI neurons, although they were not nearly as prevalent. These results demonstrate that the seizure-induced FI neurons in this area are neurons of the LPBsl and not cholinergic neurons of the PPTn-pc. This is the first report of seizure-induced Fos expression specifically localized to the superior lateral subnucleus of the lateral parabrachial area.
 ...
PMID:Expression of Fos in the superior lateral subdivision of the lateral parabrachial (LPBsl) area after generalized tonic seizures in rats. 982 Jul 33


1 2 Next >>