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)

Calcitonin gene-related peptide (CGRP)-immunoreactive afferent nerve fibers are abundant in the rat penis. In addition, NADPH-diaphorase, which stains for nitric oxide synthase, has been localized within both autonomic and sensory dorsal root ganglia (DRG) and may be part of an important biochemical pathway involved in penile tumescence. The purpose of this study was: 1) to examine the circuitry of afferent nerves that are CGRP immunoreactive from the L6 DRG, 2) to examine the possibility that there are NADPH-diaphorase-positive afferent fibers from the L6 DRG to the rat penis, and 3) to examine the localization and colocalization of CGRP and NADPH-diaphorase within L6 DRG afferent perikarya. Calcitonin gene-related peptide immunostaining in the penis was eliminated following a bilateral transection of the pudendal nerves, but was unchanged following a bilateral transection of the pelvic splanchnic or hypogastric nerves. The NADPH-diaphorase staining was not altered by any of the nerve transections. Injection of the retrograde axonal tracer fluorogold (FG) into the dorsum penis labeled perikarya in the L6 DRG. Although the majority of FG-labeled perikarya contained neither CGRP nor NADPH-diaphorase, small subpopulations of perikarya contained either CGRP immunoreactivity, NADPH-diaphorase, or both. A unilateral pudendal nerve transection virtually eliminated (> 99%) FG labeling in the ipsilateral L6 DRG. These data suggest that NADPH-diaphorase and CGRP are present, either together or separately, within a subpopulation of penile afferent perikarya. In addition, CGRP-immunoreactive afferent nerve fibers reach the penis primarily via the pudendal nerves. Finally, NADPH-diaphorase-positive penile afferents may be another important source of nitric oxide (NO) for penile tumescence.
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PMID:CGRP immunoreactivity and NADPH-diaphorase in afferent nerves of the rat penis. 149 3

The neuronal influence on the resistance of cerebral arteries was analyzed in middle cerebral arteries of guinea pigs. Calcitonin gene-related peptide- and vasoactive intestinal peptide-immunoreactive nerves and NADPH-diaphorase-positive nerves were present in the distal portion of the middle cerebral artery. Isolated middle cerebral arteries were cannulated and perfused at a constant flow rate (1 ml/min) and the perfusion pressure was monitored. Prostaglandin F2 alpha (PGF2 alpha) and K+ (50 mM) elicited a sustained increase of the perfusion pressure (vasoconstriction), while noradrenaline and 5-hydroxytryptamine caused only a slight constriction. Electrical field stimulation (FS) at 8 Hz did not elicit a contractile response. In tissues precontracted with PGF2 alpha, FS induced a tetrodotoxin-sensitive vasodilator response. Endothelium-denudation and removal of the effect of sensory nerves by capsaicin-treatment did not affect the FS-induced vasodilation. In contrast, nitro-L-arginine, an inhibitor of NO formation, attenuated the FS-induced vasodilatation. These results show that the resistance of the cerebral vessels of guinea pigs is under the influence of vasodilator nerves and that the neurogenic vasodilator mechanism involves NO synthesis.
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PMID:Vasodilator innervation of small cerebral arteries of guinea pigs. 783 88

We previously demonstrated calcitonin gene-related peptide (CGRP) immunoreactivity in sensory nerves in the rat uterus and that CGRP inhibits stimulated uterine contraction in vitro. The present study was undertaken to: 1) examine possible roles nitric oxide (NO) may have in the inhibitory action of CGRP on uterine contraction and 2) identify sites where NO may be synthesized. The relaxing effect of CGRP on SP-stimulated uterine contraction was established in vitro on uterine horns from diethylstilbestrol-treated rats. These experiments were repeated with or without an arginine analog [NG-monomethyl-L-arginine (L-NMMA)] that inhibits NO formation. The localization of the synthetic enzyme for NO production, NO synthase, was accomplished by histochemically staining for NADPH-diaphorase. Calcitonin gene-related peptide (10(-7) M) significantly reduced SP (10(-5) or 10(-6) M)-stimulated uterine contraction. The L-NMMA (10(-3) M) blocked the relaxing action of CGRP on SP-stimulated uterine contraction. The L-NMMA alone had no effect on SP-stimulated uterine contraction. NADPH-diaphorase-positive nerve fibers were located in the myometrium, endometrium, and adjacent to the vasculature. These data demonstrate that: 1) L-NMMA suppresses the relaxant effect of CGRP on myometrial activity and 2) NADPH-diaphorase (indicative of NO synthase) is localized in uterine nerve fibers. These data suggest that the inhibitory action of CGRP may be dependent on NO formation and that the enzyme necessary for NO production is present in nerves in areas optimal to affect myometrial activity.
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PMID:NADPH-diaphorase-positive nerves and the role of nitric oxide in CGRP relaxation of uterine contraction. 833 59

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.
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PMID:Cyclic AMP induces a relaxation response in the bullfrog Rana catesbeiana, but nitric oxide does not. 935 74

The distribution of nitrergic neurons was investigated by using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and nitric oxide synthase (NOS) immunohistochemistry in wholemount preparations of the urinary bladder in guinea pigs. Both NADPH-d+ and NOS+ neurons were located predominantly in the bladder base. Double staining showed that 70.9% of the NADPH-d+ neurons coexpressed NOS. Acetylcholinesterase histochemistry revealed that a majority of the intramural neurons were reactive, and about half of them (51.4%) were double labelled for NOS. Tyrosine hydroxylase-positive neurons were also distributed mainly in the bladder base but in a neuronal population that was separate from the preponderant NADPH-d+ neurons. Vasoactive intestinal polypeptide immunoreactivity was also detected in the some of intramural ganglion cells, in which 21.3% of them coexpressed NADPH-d. Calcitonin gene-related peptide and substance P immunoreactivities were confined to nerve fibers, often in close association with NADPH-d+ cells or extended along the blood vessels. These results have demonstrated the colocalization of NADPH-d and NOS in the majority of intramural ganglion cells. Many of the nitrergic neurons are apparently cholinergic, indicating that they are parasympathetic postganglionic neurons, and this underscores NO as the major neuromodulator in the parasympathetic nerves in the bladder walls. The localization of vasoactive intestinal polypeptide in nitrergic neurons suggests that the peptide may complement NO for regulation of micturition reflex. The close relationship of NADPH-d-reactive intramural neurons with calcitonin gene-related peptide and substance P fibers, most probably derived from dorsal root ganglion cells, suggests that NO released from the local neurons may exert its influence on the sensory neural pathways in the urinary bladder.
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PMID:Colocalization of nitric oxide synthase and some neurotransmitters in the intramural ganglia of the guinea pig urinary bladder. 959 May 57

The distribution and role of neurotransmitters and neuromodulators in laryngeal innervation are reviewed, and our recent findings regarding the nitrergic innervation of the larynx are demonstrated for the better understanding of the complexity of the laryngeal innervation system. Noradrenergic innervation of the larynx was studied with fluorescence histochemistry and electron microscopy after application of 5-hydroxydopamine. These studies confirmed the existence of noradrenergic innervation for the submucosal glands and blood vessels, and the origin and course of noradrenergic nerve fibers contained in the laryngeal nerves and their destinations in the larynx. Cholinergic innervation of the larynx has not been clarified in detail. Many kinds of neuropeptides have been demonstrated to be involved in laryngeal innervation. Vasoactive intestinal polypeptide originating from intralaryngeal ganglionic neurons participates in laryngeal vasodilation and reduction of laryngeal seromucous secretion. Neuropeptide Y nerve fibers are few in the larynx, and most originate from the superior cervical ganglion. They are distributed around the large or medium-sized blood vessels, especially arteries. They are also associated with excretory structures. Substance P was the first neuropeptide found to be a sensory neurotransmitter in the laryngeal afferent system. It is also involved in regulation of laryngeal blood flow and secretion. Calcitonin gene-related peptide is associated with the sensory, autonomic, and motor innervation of the larynx. The majority of enkephalin nerve fibers are located close to excretory structures, although no information on the physiological significance of enkephalin is available. In addition to the above neuropeptides, the peptides histidine isoleucine, histidine methionine, and helospectin have been shown to exist in the larynx. The nitrergic innervation of the larynx has been recently studied with NADPH-diaphorase histochemistry and immunohistochemistry using antiserum against nitric oxide synthase. Nitric oxide originates from the neurons in the intralaryngeal ganglia and is believed to modulate blood flow and secretion of the larynx. It controls the laryngeal exocrine secretion in cooperation with intrinsic vasoactive intestinal polypeptide and/or extrinsic calcitonin gene-related peptide. Nitric oxide from the nodose ganglion may modulate nociception of the larynx. The existence of nitrergic neurons located in the intrinsic laryngeal muscles has been demonstrated. Many of them are bipolar or pseudounipolar, so they might be sensory in nature. The effect of injury of the recurrent laryngeal nerve on the induction of nitric oxide synthase in the laryngeal motoneurons is also discussed.
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PMID:Neurotransmitters and neuromodulators involved in laryngeal innervation. 1115 58

The vascular supply of the optic nerve has been studied with different methods including corrosion casts both in humans and in other mammals. In man, primates and some other mammals, such as the rat, a distinct central retinal artery accompanies the optic nerve, and runs through the lamina cribosa to reach the optic nerve head. Similarities between human and rat central retinal artery could serve to understand changes in the autonomic perivascular innervation in glaucoma using the rat as an animal model. Nitric oxide, calcitonin gene-related peptide, neuropeptide Y, substance P and vasoactive intestinal peptide have been identified around the monkey central retina artery. Innervation of the rat central artery, however, has not been described in detail. Using immuno- and histochemical methods, the present study investigates the peptidergic, adrenergic and nitrergic innervation of the rat posterior ciliary artery as well as the central retina artery. Numerous nitric oxide positive nerve fibers were visualized posterior and anterior to the lamina cribosa of the optic nerve. They colocalized with NADPH-diaphorase positive fibers, which could also be observed in two of six specimens studied at the level of the optic nerve head. Calcitonin gene-related peptide, tyrosine hydroxylase, and VIP positive fibers were also observed surrounding the vessels of the rat optic nerve. The presence of neuronal nitric oxide/NADPH-diaphorase and vasoactive intestinal peptide positive nerve fibers surrounding the posterior ciliary and central retinal arteries indicates a vasodilator effect in the rat optic nerve. Tyrosine hydroxylase positive innervation indicates the presence of sympathetic activity, and calcitonin gene-related peptide positive fibers indicate sensory innervation by trigeminal primary efferents.
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PMID:Vasoactive intestinal and calcitonin gene-related peptides, tyrosine hydroxylase and nitrergic markers in the innervation of the rat central retinal artery. 1290 69

The small and large intestine of adult horses were histochemically and immunohistochemically investigated in order to evidence components of the intramural nervous system. The general structural organization of the intramural nervous system was examined by using Nissl-thionin staining as well as the anti-neurofilament 200 (NF200) immunoreaction, which demonstrated the presence of neurons in the submucous as well as myenteric plexuses. The additional presence of subserosal ganglia was shown in the large intestine. Acetylcholinesterase (AChEase) activity was observed in both the submucous and myenteric plexuses. Localization of acetylcholine-utilizing neurons was also evidenced by immunohistochemical reactions for choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT). With both histochemistry and immunohistochemistry possible cholinergic nerve fibres were detected in the inner musculature. The two possible cholinergic co-mediators Calcitonin Gene-Related Peptide (CGRP) and Substance P (SP) have been investigated by an immunohistochemical approach. CGRP immunoreactivity was detected in roundish nerve cell bodies as well as in nerve fibres of the submucous plexus, whereas SP immunoreactivity was evidenced in nerve fibres of the tunica mucosa, in nerve cell bodies and fibres of the submucous plexus and in nerve fibres of the myenteric plexus. NADPH-diaphorase reactivity, which is linked to the synthesis and release of nitric oxide, was detected in nerve cell bodies and nerve fibres of both the submucous and myenteric plexuses as well as in a subserosal localization of the large intestine. The nitrergic components were confirmed by the anti-NOS (nitric oxide synthase) immunoreaction. Results are compared with those of other mammals and related to the complex intestinal horse physiology and pathophysiology.
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PMID:Cholinergic, nitrergic and peptidergic (Substance P- and CGRP-utilizing) innervation of the horse intestine. A histochemical and immunohistochemical study. 1502 97