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)

The innervation of the cat lower oesophagus, including the lower oesophageal sphincter, was studied by enzyme histochemistry, immunohistochemistry, and confocal microscopy. In the lower oesophageal sphincter, and at a level 2 cm above it, no apparent differences were seen in the nerve distribution pattern. Among the nerve populations studied, acetylcholinesterase (AChE)-positive nerves were the most abundant in both these regions. The density of AChE-positive nerves was particularly marked in the circular muscle layer. A rich supply of nitric oxide synthase (NOS)-containing nerves was identified by using an antiserum against neuronal NOS, or by enzyme histochemical staining for NADPH diaphorase activity. Vasoactive intestinal peptide (VIP)-immunoreactive nerves had a similar distribution pattern as NOS-immunoreactive nerves, and nerves displaying immunoreactivity for NOS and VIP often showed profiles coinciding with AChE-positive nerves. As judged by confocal microscopy, immunoreactivities for helospectin, pituitary adenylate cyclase-activating peptide (PACAP) and VIP, to a large extent were found in the same nerves. At a level 7 cm above the lower oesophageal sphincter, the total nerve supply was less than in the sphincter itself and 2 cm above it. Immunoreactivity towards VIP, PACAP and helospectin was also found to co-exist with NOS and neuropeptide Y within the same nerve structures. It is concluded that there is an intricate innervation pattern in the feline lower oesophagus reflecting the complexity in the regulation of its motility.
 ...
PMID:Nitric oxide synthase-containing, peptide-containing, and acetylcholinesterase-positive nerves in the cat lower oesophagus. 753 Nov 90

The distribution and colocalization of nitrinergic and peptidergic nerves were examined in six human colons. The tissues were fixed, cryosectioned, and standard immunohistochemistry was performed for several known neuropeptides. The same sections were stained for NADPH-diaphorase to denote nitric oxide synthase. NADPH-diaphorase-positive myenteric neurons were counted and colocalization noted for each peptide, as well as for peptide terminations. Galanin was the only neuropeptide that colocalized to a significant extent (23.0 +/- 7.21%) with NADPH-diaphorase-positive myenteric neurons. Many neuropeptide-containing nerve fibers had extensive terminations onto NADPH-diaphorase-positive neurons. Vasoactive intestinal peptide was the only neuropeptide that colocalized with NADPH-diaphorase to any extent in nerve fibers within circular muscle (59.5 +/- 9.3%). Fiber distribution in the longitudinal muscles showed a similar, but less dense pattern. These observations provide morphological evidence for the presence of nitric oxide, a candidate nonadrenergic noncholinergic neurotransmitter in the human colon.
 ...
PMID:Nitrinergic and peptidergic innervations and their inter-relationships in human colon. 756 7

We reported decreased vasoactive intestinal peptide levels in acquired megacolon. The origin of altered neuropeptide levels is unknown, but recent work suggested that tissue antioxidants may function as neuroprotectants. Our hypothesis was that altered levels of inhibitory neurotransmitters in human colon are associated with depletion of the tripeptide thiol, glutathione. Normal colon samples (N = 10; from patients 41-80 years old) and acquired megacolon samples (N = 10; from patients 31-98 years old) were obtained at surgery. Vasoactive intestinal peptide levels were decreased in muscularis externa from acquired megacolon (P = 0.01), while there was a modest increase in NADPH diaphorase activity in muscularis externa from megacolon (P = 0.10). Glutathione in acquired megacolon was detectable in muscularis externa from only five specimens (P < 0.05), but was not significantly different (P > 0.05) in the mucosal-submucosal layer. The results supported the presence of vasoactive intestinal peptide and NADPH diaphorase in distinct subpopulations of nerves in human colon. The results also supported the hypothesis that glutathione functions as a neuroprotectant in a subset of patients with acquired megacolon.
 ...
PMID:Decreased vasoactive intestinal peptide levels and glutathione depletion in acquired megacolon. 868 18

Glutathione is a nonenzymatic antioxidant synthesized by most animal cells and is depleted in inflammatory bowel disease. The effects of glutathione depletion on intestinal histology and inhibitory neurochemicals was examined in a mouse model. Glutathione depletion in A/J mice involved inhibition of gamma-glutamylcysteine synthetase using L-buthionine-(S,R)-sulfoximine (BSO) for 10 days. Ileum and colon were obtained from saline-control mice, BSO-treated mice, and BSO-treated mice receiving ascorbate or glutathione monoethylester. Glutathione, lipid peroxides, and nicotineamide adenine dinucleotide phosphate diaphorase activity were measured by colorimetric assays. Vasoactive intestinal peptide was measured by radioimmunoassay. Glutathione depletion induced enlargement of mucosal-submucosal lymphoid aggregates without germinal centers in ileum and colon. These aggregates were prevented by supplementation with glutathione monoethylester but not ascorbate. Tissue levels of inhibitory neurochemicals were unchanged. Depletion of glutathione appears to induce enlarged lymphoid aggregates by recruitment of lymphocytes from the peripheral circulation. A component of the inflammation that develops in inflammatory bowel disease could be related to depletion of tissue levels of glutathione.
 ...
PMID:Induction of enlarged intestinal lymphoid aggregates during acute glutathione depletion in a murine model. 1121 24

Neurotransmitters mediating nonadrenergic-noncholinergic (NANC) relaxation were investigated in strips of porcine retractor penis muscle (RPM). Muscle tone was raised by phenylephrine (1 microM) in the presence of atropine (1 microM) and guanethidine (50 microM). Upon electrical field stimulation (1 ms, 80 V, 1-32 Hz for 10 s), the initial fast relaxation was followed by the slow relaxation. Although the fast and the slow relaxation were completely abolished by tetrodotoxin (1 microM), they showed different pharmacological sensitivities to the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 0.1 mM). The fast relaxation was markedly inhibited by L-NAME in an L-arginine reversible manner and by oxyhemoglobin (50 microM), while the slow relaxation was hardly blocked by L-NAME. L-NAME and alpha-chymotrypsin (alpha-CT, 3 U/ml) selectively inhibited the fast and the slow relaxation, respectively. Alpha-CT abolished L-NAME-resistant slow relaxation, and L-NAME completely abolished the alpha-CT-resistant fast relaxation. Alpha-CT-resistant relaxation was not significantly different from the digitally calculated L-NAME-sensitive component, and L-NAME-resistant relaxation was similar to the digitally calculated alpha-CT-sensitive component. Vasoactive intestinal peptide (VIP, 0.003-0.1 microM) relaxed porcine RPM in a concentration-dependent manner. The effect of a VIP was partially inhibited by a VIP receptor antagonist, VIP(10-28) (1 and 3 microM). L-NAME-resistant relaxation was also reduced by VIP(10-28) (3 microM) and by another putative antagonist, VIP(6-28) (1 microM), although the effects of the two antagonists were somewhat inconsistent. From the histochemical staining, it was verified that nerve bundles that showed VIP-like immunoreactivities were also positive for the NADPH diaphorase reaction. These results suggest that NO and peptide neurotransmitter(s) including VIP mediate the NANC relaxation in porcine RPM.
 ...
PMID:Involvement of nitric oxide and vasoactive intestinal peptide in the nonadrenergic-noncholinergic relaxation of the porcine retractor penis muscle. 1145 27