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)

Nitric oxide (NO) has been shown to play a significant role in inflammation. To clarify the role of NO in acute pancreatitis, we investigated the serum concentrations of NO chi (NO2- plus NO3-) and tumor necrosis factor-alpha (TNF-alpha) and the grade of pancreatitis in cerulein-induced pancreatitis in mice pretreated with lipopolysaccharide (LPS) or not. LPS pretreatment aggravated the cerulein pancreatitis in association with a transient increase in serum TNF-alpha, which was followed by a gradual elevation of serum NO chi. This elevation of serum NO chi concentration was inhibited by the NO synthase inhibitor NG-nitro-L-arginine (L-NNA). In addition, the activity of NADPH-diaphorase (NADPH-d), a marker for NO synthase, appeared in the peritoneal macrophages of LPS-pretreated mice after the induction of pancreatitis. No elevation of serum NO chi or appearance of NADPH-d activity in peritoneal cells was found in mice without LPS pretreatment. Administration of L-NNA enhanced the elevation of pancreatitis-induced serum amylase in mice untreated with LPS, while L-NNA inhibited the elevation in LPS-pretreated mice. The effects of L-NNA were reversed by the administration of L-arginine but were not affected by D-arginine. These results suggested that (a) inflammatory cells may not be fully activated to produce excessive NO in uncomplicated edematous pancreatitis, and (b) edematous pancreatitis may be aggravated by excessively produced NO if bacterial infection is complicated and inflammatory cells are activated to express inducible NO synthase.
Pancreas 1996 Jan
PMID:The role of nitric oxide in mouse cerulein-induced pancreatitis with and without lipopolysaccharide pretreatment. 892 22

Glutamate and related molecules are the major excitatory neurotransmitters in the central nervous system, and their receptors have been localized therein. Little is, however, known about them in the peripheral nervous system. The present study investigated the localization of glutamate receptor subunits of the alpha-amino-3-hydroxy- 5-methyl-4-isoxazolepropionate (AMPA) type (GluR1, GluR2-3, and GluR4) in the pancreas of newborn guinea pigs. With a double-labeling method of immunofluorescence and immuno-tetrahydrochloride reaction, GluR1 and GluR4 immunoreactivities were localized mostly in the insulin-secreting cells in the central mass of the islet, and GluR2-3 immunoreactivity in the peripheral rim of the islet, which consists mainly of non-insulin-secreting islet cells. With a double-labeling method employing immunofluorescence and NADPH-diaphorase (NADPH-d) histochemistry, GluR2-3 and GluR4 immunoreactivities were localized in most of the NADPH-d positive pancreatic ganglion cells. None of the NADPH-d-positive ganglion cells showed GluR1 immunoreactivity. In fact, GluR1 immunoreactivity was not detected in any of the pancreatic ganglion cells. The results indicate that glutamate is likely to exert its effects on the pancreas by activating different AMPA receptor subunits located in endocrine cells and intrapancreatic ganglia.
Pancreas 1997 May
PMID:Localization of glutamate receptor subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type in the pancreas of newborn guinea pigs. 916 82

Stimulation of extrinsic nerves markedly alters pancreatic endocrine and exocrine secretion, yet little is known of the neurochemical organization and physiologic roles of specific neural pathways within the pancreas. Here we report histochemical staining for acetylcholinesterase (AChE), NADPH-diaphorase (NADPH-d), nitric oxide synthase (NOS), and several neuropeptides to identify the neurotransmitter content of rabbit pancreatic nerves. An extensive network of AChE-positive nerve fibers was found throughout the islets, acini, ducts, ganglia, and blood vessels. All pancreatic neurons were AChE positive, two thirds were NADPH-d positive, and many were NOS positive. Ganglia in the head/neck region were connected to the duodenal myenteric plexus by AChE- and NADPH-d-positive fibers, and NADPH-d-positive pancreatic neurons appeared to send processes toward both the duodenum and pancreas. Many pancreatic neurons were vasoactive intestinal peptide (VIP) positive, and VIP nerve terminals were abundant in ganglia, acini, islets, and ducts. Pituitary adenylate cyclase-activating peptide (PACAP-38)-positive fibers also were observed within acini and passing through ganglia. Substance P (SP)-, calcitonin gene-related peptide (CGRP)-, and dopamine beta-hydroxylase (DBH)-positive fibers were abundant along blood vessels and ducts, and varicose fibers were observed in pancreatic ganglia. Fine galanin-positive fibers were also occasionally observed running with blood vessels and through ganglia. Thus the rabbit pancreas receives a dense, diverse innervation by cholinergic, adrenergic, and peptidergic nerves and cholinergic pancreatic neurons, most also containing VIP or NOS or both, appear to innervate both endocrine and exocrine tissue, and may mediate local communication between the duodenum and pancreas.
Pancreas 1999 Jan
PMID:Morphology and histochemistry of the rabbit pancreatic innervation. 988 61

Pancreatic neurons receive and integrate synaptic input from a wide variety of extrinsic nerves while providing the predominant innervation of pancreatic acini, ducts, and islets of Langerhans. Here we report the first primary cultures of adult rabbit pancreatic neurons, isolated from extrinsic nerves and secretory cells, and evaluate the neurochemical and electrical properties of these neurons. Pancreatic cultures consisted of single and clustered neurons, extended varicose processes after 3-4 days in culture, and formed interconnecting networks of neurons after 7-10 days. Isolated pancreatic islet cells, added to established neuron cultures, remained attached and viable for several weeks and received innervation by varicose nerve fibers. Histochemical staining revealed populations of neurons positive for acetylcholinesterase (75%), NADPH-diaphorase (62%), nitric oxide synthase (73%), and/or vasoactive intestinal peptide (VIP) (65%). Intracellular recordings revealed active and passive electrical properties comparable to those of neurons from intact ganglia. Several distinct populations of neurons were identified by their firing patterns (phasic vs. tonic) in response to prolonged depolarizing currents or the amplitude and duration of their after-spike hyperpolarizations. Low-amplitude, pacemaker-like potentials were observed in 25% of the neurons and, in older cultures with extensive networks of fibers, spontaneous fast excitatory postsynaptic potentials (EP-SPs) also occurred. Thus these cultures retained the salient neurochemical and electrophysiologic properties observed in pancreatic neurons from intact ganglia and offer a good model for studies of the intrinsic innervation of the pancreas.
Pancreas 1999 Jan
PMID:Histochemistry and electrophysiology of cultured adult rabbit pancreatic neurons. 988 62