NADPH Dehydrogenase
Myenteric Plexus
Neurons
Nitric Oxide
Characterization of the non-nitrergic NANC relaxation responses in the rabbit vaginal wall. (1/71)
Electrical field stimulation (EFS)-induced non-adrenergic non-cholinergic (NANC) relaxation responses in the rabbit vaginal wall were investigated. These NANC responses were partially inhibited with the nitric oxide synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME; 500 microM), N(G)-nitro-L-arginine (300 microM) or N-iminoethyl-L-ornithine (500 microM) or the selective soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 10 microM). Application of L-NAME and ODQ concomitantly did not increase the degree of inhibition. L-NAME or ODQ were observed to be more effective at low frequencies. The resistant part of the responses was more pronounced at higher frequencies and was completely inhibited by tetrodotoxin (1 microM). Exogenous application of the peptides vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide (PACAP-27 and PACAP-38), peptide histidine methionine (PHM), peptide histidine valine (PHV), helospectin-I or -II induced a relaxation response. Calcitonin gene-related peptide or substance P did not cause any relaxation. The peptidase alpha-chymotrypsin (type II; 2 units ml(-1)) did not affect non-nitrergic NANC responses, although it did inhibit relaxation responses elicited by exogenous VIP, PACAP-27, PACAP-38, PHM, PHV, helospectin-I or -II. K(+) channel inhibitors apamin (1 microM) or charybdotoxin (100 nM) when used alone or in conjunction did not affect non-nitrergic NANC responses. The non-nitrergic NANC responses were not associated with any increase in intracellular cyclic adenosine-3', 5'-monophosphate (cyclic AMP) or cyclic guanosine-3', 5'-monophosphate (cyclic GMP) concentrations. The peptide-induced relaxations were all associated with increases in cyclic AMP concentrations. These results suggest that a neuronal factor elicits non-nitrergic NANC responses in the rabbit vaginal wall. The identity of this factor remains to be established. (+info)Neurogenic cerebral vasodilation mediated by nitric oxide. (2/71)
In cerebral arteries isolated from most of mammals, nerve stimulation produces relaxations in contrast to contractions in peripheral arteries. The relaxant mechanism is found to be non-adrenergic and non-cholinergic, but the neurotransmitter is not clarified until recently. Based on several functional and histological studies with isolated cerebral arteries, nitric oxide (NO) is now considered to be a neurotransmitter of the vasodilator nerve and the nerve has been called a nitroxidergic (nitrergic) nerve. Upon neural excitation, calcium influxed through N-type Ca2+ channels activates neuronal NO synthase, and then NO is produced by the enzyme from L-arginine. The released NO activates soluble guanylate cyclase in smooth muscle cells, resulting in relaxation with a cyclic GMP-dependent mechanism. The functional role and neuronal pathway have also been investigated in anesthetized dogs and Japanese monkeys. The nitroxidergic (nitrergic) nerves innervating the circulus arteriosus, including the anterior and middle cerebral and posterior communicating arteries, are found to be postganglionic nerves originated from the ipsilateral pterygopalatine ganglion and tonically dilate cerebral arteries in the resting condition. Our findings suggest that the nitroxidergic (nitrergic) nerve plays a physiologically important role to maintain a steady blood supply to the brain. (+info)Sympathetic modulation of nitrergic neurogenic vasodilation in cerebral arteries. (3/71)
The presence of close apposition between the adrenergic and the non-adrenergic or nitrergic nerve terminals in large cerebral arteries in several species is well documented. The axo-axonal distance between these different types of nerve terminals is substantially closer than the synaptic distance between the adventitial nerve terminals and the outermost layer of smooth muscle in the media. This feature suggests that a functional axo-axonal interaction between nerve terminals is more likely to occur than that between the nerve and muscle. Thus, transmitters released from one nerve terminal may modulate release of transmitters from the neighboring nerve terminals, resulting in a neurogenic response. We have reported that nicotine-induced nitric oxide (NO)-mediated neurogenic vasodilation is dependent on intact sympathetic innervation in porcine and cat cerebral arteries. Evidence also has been presented to indicate that nicotine acts on alpha7-nicotinic receptors located on sympathetic nerve terminals, resulting in release of norepinephrine which then diffuses to act on beta2-adrenoceptos located on the neighboring nitrergic nerve terminals to release NO and therefore vasodilation. The predominant facilitatory effect of beta2-adrenoceptors in releasing NO is compromised by presynaptic alpha2-adrenoceptors located on the same nerves. Activation of cerebral sympathetic nerves may cause NO-mediated dilation in large cerebral arteries at the base of the brain. (+info)Reduced number of intrinsic pulmonary nitrergic neurons in Fawn-Hooded rats as compared to control rat strains. (4/71)
The Fawn-Hooded rat (FHR) strain reveals a congenital predisposition to primary (idiopathic) pulmonary hypertension (PPH), and can therefore be regarded as an animal model in which to study possible mechanisms underlying an inherited susceptibility to pulmonary hypertension. Pulmonary hypertension can be induced in FHRs after a short exposure to mild hypoxia, presumably because of an altered peripheral oxygen sensitivity. Given the presence of pulmonary nitrergic neurons in rat lungs, the observed link between airway hypoxia and the expression of pulmonary neuronal nitric oxide synthase (nNOS), and the fact that nNOS appears to be involved in peripheral chemoreceptor sensitivity, we examined the intrinsic pulmonary nitrergic innervation in the FHR. In the present study the number of intrapulmonary nitrergic nerve cell bodies, detected by NADPH diaphorase (NADPHd) histochemistry, was quantified in the FHR and three control rat strains. Compared to the control rat strains, the FHR lungs revealed a highly significantly lower number of intrinsic nitrergic neurons, while no apparent differences were found in the number of enteric nitrergic neurons in the esophagus. In conclusion, the possible links between neuronal NO, hypersensitivity to airway hypoxia, and the development of PPH clearly deserve further investigation. (+info)Role of intrinsic nitrergic neurones on vagally mediated striated muscle contractions in the hamster oesophagus. (5/71)
Oesophageal peristalsis is controlled by vagal motor neurones, and intrinsic neurones have been identified in the striated muscle oesophagus. However, the effect(s) of intrinsic neurones on vagally mediated contractions of oesophageal striated muscles has not been defined. The present study was designed to investigate the role of intrinsic neurones on vagally evoked contractions of oesophageal striated muscles, using hamster oesophageal strips maintained in an organ bath. Stimulation (30 micros, 20 V) of the vagus nerve trunk produced twitch contractions. Piperine inhibited vagally evoked contractions, while capsaicin and NG-nitro-L-arginine methyl ester (L-NAME) abolished the inhibitory effect of piperine. The effect of L-NAME was reversed by subsequent addition of L-arginine, but not by D-arginine. L-NAME did not have any effect on the vagally mediated contractions and presumed 3H-ACh release. NONOate, a nitric oxide donor, and dibutyryl cyclic GMP inhibited twitch contractions. Inhibition of vagally evoked contractions by piperine and NONOate was fully reversed by ODQ, an inhibitor of guanylate cyclase. Immunohistochemical staining showed immunoreactivity for nitric oxide synthase (NOS) in nerve cell bodies and fibres in the myenteric plexus and the presence of choline acetyltransferase and NOS in the motor endplates. Only a few NOS-immunoreactive portions in the myenteric plexus showed vanilloid receptor 1 (VR1) immunoreactivity. Our results suggest that there is a local neural reflex that involves capsaicin-sensitive neurones, nitrergic myenteric neurones and vagal motor neurones. (+info)Spatial pattern analysis of nitrergic neurons in the developing myenteric plexus of the human fetal intestine. (6/71)
BACKGROUND: Enteric nervous system precursors derived from the neural crest migrate along defined pathways to colonize the bowel. The individual cells in different environments experience different growth, differentiation, and survival conditions. Hence, the spatial distribution of the neurons is determinant with regard to functional maturation. The question arises as to whether the distribution is random or nonrandom. METHODS: Nitrergic cells were visualized by means of nicotinamide adenine dinucleotide phosphate diaphorase histochemistry. Stained specimens were photographed, and the borders of the myenteric plexus and the nuclei of the nitrergic neurons were digitalized. Plexus Pattern Analysis software was used to count the nuclei of nitrergic neurons, calculate the proportions of the areas covered by the plexus and the gut wall, and perform randomization analyses. RESULTS: The distribution pattern of the nitrergic neurons changed markedly between weeks 14 and 22 of gestation. The nitrergic neurons were randomly distributed at week 14 but were aggregated in the plexus and within the individual ganglia at week 19. The dynamics of these changes exhibited regional differences. CONCLUSIONS: The results suggest that, in addition to the gut wall and the plexus, other intraganglionic constituents may contribute to the aggregation of nitrergic cells and such examinations should be extended to other cell types in the future. (+info)Changes in the number of nitrergic neurons following kainic acid administration and repeated long-term hypoxia. (7/71)
Using histochemical analysis (NADPH-diaphorase) we have been investigating the influence of intraperitoneal administration of kainic acid (KA), hypoxia and combination of both these factors on neurons of the hippocampus and on the primary auditory cortex (PAC) in male rats of the Wistar strain. Kainic acid was administered to 18-day-old animals, which were exposed to long-lasting repeated hypoxia from the 2nd till the 17th day of age in a hypobaric chamber (for 8 h a day). At the age of 22 or 90 days, the animals were transcardially perfused with 4 % paraformaldehyde under deep thiopental anesthesia. Cryostate sections were stained to identify NADPH-diaphorase positive neurons that were then quantified in the hippocampus, in the dentate gyrus and in the PAC. In 22-day-old animals both hypoxia and KA increased the number of NADPH-diaphorase positive neurons in the hilus, CA1, CA3 areas of the hippocampus and in the PAC. On the contrary, KA given to hypoxic animals lowered the number of NADPH-diaphorase positive neurons in the dentate gyrus. In 90-day-old animals, hypoxia and KA given to both normoxic and hypoxic animals lowered the number of NADPH-diaphorase positive neurons in some areas of the central nervous system. (+info)Adrenergic, nitrergic and peptidergic innervation of the urethral muscle in the boar. (8/71)
In this study, the innervation of the urethral muscle in adult male pigs was investigated using combined NADPH-diaphorase (NADPH-d) histochemistry and immunocytochemistry. Nerve fibres supplying the urethral muscle were found to show NADPH-d activity and they also expressed immunoreactivity to catecholamine synthesising enzymes including tyrosine hydoxylase (TH) and dopamine-beta-hydroxylase (DbetaH) as well as to: vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY). Different subpopulations of the nerve fibres (NADPH-d positive, TH-, DbetaH-, VIP- and NPY-immunoreactive (IR), but also NADPH-d/VIP- and NADPH-d/NPY-IR) were disclosed. These nerve fibres were observed not only to run among muscle fibres of the urethral muscle, but also within extrinsic nerve trunks. Moreover, in the organ studied, numerous ganglia were found. The intramural ganglia, composed of a few to 30 neurons were located in the proximal, middle and distal regions of the pelvic urethra. In the vicinity of the urethral muscle, there were mainly small ganglia containing two to several neurons, but also larger ganglia consisting of up to tens neurons were encountered in the connective tissue surrounding the pelvic urethra. In the ganglia observed in the neighbourhood of the urethral muscle, different subpopulations of nerve cells were found, namely: catecholaminergic, nitrergic, VIP-IR, NPY-IR and also NADPH-d/DbetaH-, NADPH-d/VIP- and NADPH-d/NPY-positive. Possible sources of the innervation for this muscle were also discussed. (+info)Nitrergic neurons are specialized cells within the nervous system that release nitric oxide (NO) as their primary neurotransmitter. Nitric oxide is a small, gaseous molecule that plays an essential role in various physiological processes, including neurotransmission, vasodilation, and immune response.
In the context of the nervous system, nitrergic neurons are involved in several functions:
1. Neurotransmission: Nitric oxide acts as a retrograde messenger, transmitting signals backward across synapses to modulate the activity of presynaptic neurons. This unique mode of communication allows for fine-tuning of neural circuits and contributes to various cognitive processes, such as learning and memory.
2. Vasodilation: Nitrergic neurons are present in blood vessel walls, where they release nitric oxide to cause vasodilation. This process helps regulate blood flow and pressure in different organs and tissues.
3. Immune response: Nitrergic neurons can interact with immune cells, releasing nitric oxide to modulate their activity and contribute to the body's defense mechanisms.
4. Gastrointestinal motility: In the gastrointestinal tract, nitrergic neurons are involved in regulating smooth muscle contractility and relaxation, which influences gut motility and secretion.
5. Reproductive system function: Nitrergic neurons play a role in the regulation of sexual behavior, penile erection, and sperm motility in the male reproductive system.
It is important to note that nitrergic neurons can be found throughout the nervous system, including the central and peripheral nervous systems, and are involved in various physiological processes. Dysfunction of these neurons has been implicated in several pathological conditions, such as neurodegenerative diseases, cardiovascular disorders, and gastrointestinal motility dysfunctions.
NADPH Dehydrogenase (also known as Nicotinamide Adenine Dinucleotide Phosphate Hydrogen Dehydrogenase) is an enzyme that plays a crucial role in the electron transport chain within the mitochondria of cells. It catalyzes the oxidation of NADPH to NADP+, which is a vital step in the process of cellular respiration where energy is produced in the form of ATP (Adenosine Triphosphate).
There are multiple forms of this enzyme, including both membrane-bound and soluble varieties. The membrane-bound NADPH Dehydrogenase is a complex I protein found in the inner mitochondrial membrane, while the soluble form is located in the cytosol.
Mutations in genes encoding for this enzyme can lead to various medical conditions, such as mitochondrial disorders and neurological diseases.
The myenteric plexus, also known as Auerbach's plexus, is a component of the enteric nervous system located in the wall of the gastrointestinal tract. It is a network of nerve cells (neurons) and supporting cells (neuroglia) that lies between the inner circular layer and outer longitudinal muscle layers of the digestive system's muscularis externa.
The myenteric plexus plays a crucial role in controlling gastrointestinal motility, secretion, and blood flow, primarily through its intrinsic nerve circuits called reflex arcs. These reflex arcs regulate peristalsis (the coordinated muscle contractions that move food through the digestive tract) and segmentation (localized contractions that mix and churn the contents within a specific region of the gut).
Additionally, the myenteric plexus receives input from both the sympathetic and parasympathetic divisions of the autonomic nervous system, allowing for central nervous system regulation of gastrointestinal functions. Dysfunction in the myenteric plexus has been implicated in various gastrointestinal disorders, such as irritable bowel syndrome, achalasia, and intestinal pseudo-obstruction.
Neurons, also known as nerve cells or neurocytes, are specialized cells that constitute the basic unit of the nervous system. They are responsible for receiving, processing, and transmitting information and signals within the body. Neurons have three main parts: the dendrites, the cell body (soma), and the axon. The dendrites receive signals from other neurons or sensory receptors, while the axon transmits these signals to other neurons, muscles, or glands. The junction between two neurons is called a synapse, where neurotransmitters are released to transmit the signal across the gap (synaptic cleft) to the next neuron. Neurons vary in size, shape, and structure depending on their function and location within the nervous system.
Nitric oxide (NO) is a molecule made up of one nitrogen atom and one oxygen atom. In the body, it is a crucial signaling molecule involved in various physiological processes such as vasodilation, immune response, neurotransmission, and inhibition of platelet aggregation. It is produced naturally by the enzyme nitric oxide synthase (NOS) from the amino acid L-arginine. Inhaled nitric oxide is used medically to treat pulmonary hypertension in newborns and adults, as it helps to relax and widen blood vessels, improving oxygenation and blood flow.
Nitric Oxide Synthase (NOS) is a group of enzymes that catalyze the production of nitric oxide (NO) from L-arginine. There are three distinct isoforms of NOS, each with different expression patterns and functions:
1. Neuronal Nitric Oxide Synthase (nNOS or NOS1): This isoform is primarily expressed in the nervous system and plays a role in neurotransmission, synaptic plasticity, and learning and memory processes.
2. Inducible Nitric Oxide Synthase (iNOS or NOS2): This isoform is induced by various stimuli such as cytokines, lipopolysaccharides, and hypoxia in a variety of cells including immune cells, endothelial cells, and smooth muscle cells. iNOS produces large amounts of NO, which functions as a potent effector molecule in the immune response, particularly in the defense against microbial pathogens.
3. Endothelial Nitric Oxide Synthase (eNOS or NOS3): This isoform is constitutively expressed in endothelial cells and produces low levels of NO that play a crucial role in maintaining vascular homeostasis by regulating vasodilation, inhibiting platelet aggregation, and preventing smooth muscle cell proliferation.
Overall, NOS plays an essential role in various physiological processes, including neurotransmission, immune response, cardiovascular function, and respiratory regulation. Dysregulation of NOS activity has been implicated in several pathological conditions such as hypertension, atherosclerosis, neurodegenerative diseases, and inflammatory disorders.