Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) is synthesized in neurons and is a potent relaxor of vascular and nonvascular smooth muscle. The uterus contains abundant NO-synthesizing nerves which could be autonomic and/or sensory. This study was undertaken to determine: 1) the source(s) of NO-synthesizing nerves in the rat uterus and 2) what other neuropeptides or transmitter markers might coexist with NO in these nerves. Retrograde axonal tracing, utilizing Fluorogold injected into the uterine cervix, was employed for identifying sources of uterine-projecting neurons. NO-synthesizing nerves were visualized by staining for nicotinamide adenine dinucleotide phosphate (reduced)-diaphorase (NADPH-d) and immunostaining with an antibody against neuronal/type I NO synthase (NOS). NADPH-d-positive perikarya and terminal fibers were NOS-immunoreactive (-I). Some NOS-I/NADPH-d-positive nerves in the uterus are parasympathetic and originate from neurons in the pelvic paracervical ganglia (PG) and some are sensory and originate from neurons in thoracic, lumbar, and sacral dorsal root ganglia. No evidence for NOS-I/NADPH-d-positive sympathetic nerves in the uterus was obtained. Furthermore, double immunostaining revealed that in parasympathetic neurons, NOS-I/NADPH-d-reactivity coexists with vasoactive intestinal polypeptide, neuropeptide Y, and acetylcholinesterase and in sensory nerves, NOS-I/NADPH-d-reactivity coexists with calcitonin gene-related peptide and substance P. In addition, tyrosine hydroxylase(TH)-I neurons of the PG do not contain NOS-I/NADPH-d-reactivity, but some TH-I neurons are apposed by NOS-I varicosities. These results suggest NO-synthesizing nerves in the uterus are autonomic and sensory, and could play significant roles, possibly in conjunction with other putative transmitter agents, in the control of uterine myometrium and vasculature.
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PMID:Nitric oxide nerves in the uterus are parasympathetic, sensory, and contain neuropeptides. 753 54

Nerve elements containing neuropeptides were observed by using different antisera and Avidin-Biotin-Peroxidase technique and the distribution of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), a marker for nitric oxide (NO) synthase were studied in the ampulla hepatopancreatica (sphincter of Oddi) in the cat. A large amount of NPY, VIP, Substance P, somatostatin immunoreactive nerve fibers were found in all layers. Some immunoreactive nerve cell bodies (NPY, VIP, SP), were also observed in the wall. The NADPH-d stained cell bodies could be distinguished according to their size and the number of processes into two neuronal subtypes: large neurons with many dendrites and smaller, round cells with one or two processes. 99% of the cell bodies showed pozitive reactions for NADPH-d. The nerve fibers with NADPH-d activity were found in all layers, chiefly in the muscle layers. According to the distribution of the nerve fibers and the relationship to the effector cells, it is suggested, that these neuropeptides might have an important role in the function, and the NO containing nerve fibers are responsible for the nonadrenergic and noncholinergic inhibitory function.
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PMID:[Distribution, structure and transmitter content of nerve elements affecting the function of Oddi's sphincter]. 753 14

Congenital esophageal stenosis (CES) is a rare disorder with narrowed esophageal lumen that presents as dysphagia from childhood and that is often associated with tracheobronchial remnants or webs. The pathogenesis of CES is unknown. The aim of this study was to examine the histological and immunohistochemical features of CES. Esophagi from 2 young adults with CES and 3 controls with no motility disorders underwent routine H&E staining, trichrome staining for collagen, and detailed immunocytochemical studies for general neuronal markers (protein gene product 9.5, neuron-specific enolase, and S-100) and neurotransmitters (vasoactive intestinal polypeptide, substance P, and galanin) and nitric oxide synthase by beta-nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and a specific NO synthase antibody. Quantitative experiments compared the numbers of myenteric neurons and amounts of fibers at the circular muscle. CES esophagi showed infiltration of neutrophils in the myenteric plane, without any increase in collagen. NADPH-diaphorase histochemistry showed a significant reduction of myenteric nitrinergic neurons (7 +/- 3.4 vs. 2.7 +/- 1.8 neurons per high-power field) and fibers at the circular muscle. Other peptidergic neurons studied were not significantly reduced in CES. The specific total lack of NO inhibitory innervation may be an important mechanism in the pathogenesis of stenosis and aperistalsis of the esophagus in this disorder.
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PMID:Peptidergic and nitrinergic denervation in congenital esophageal stenosis. 754 Oct

Nitric-oxide-releasing nerves regulate esophageal smooth muscle function. The density of such nerve fibers may differ in the different functional parts of the esophagus. We used both inspection and gray-scale analysis of digitized images to seek differences in density of such nerve fibers, stained for reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase), between esophageal body and esophago-gastric sphincter and between smooth muscle layers in the opossum esophagus. Sections of Swiss roll preparations of the entire organ were stained for NADPH-diaphorase and for immunoreactivity to vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), galanin (GAL), substance P (SP) and constitutive nitric oxide synthase (cNOS). In the circular muscle layer, NADPH-diaphorase-positive fibers were most abundant at the cephalic end of the esophageal body with a significant decline toward and through the esophago-gastric sphincter. In the longitudinal muscle layer and the longitudinally-oriented muscularis mucosae, NADPH-diaphorase-positive nerve fibers were most abundant at the esophago-gastric sphincter with a significant decline toward and through the striated-smooth muscle junction. cNOS immunoreactivity co-localized with NADPH-diaphorase activity. Fibers stained for CGRP immunoreactivity were distributed like the NADPH-diaphorase-positive fibers. Fibers stained for immunoreactivity to the other peptides (VIP, GAL, SP) showed no clear differences in distribution along the esophagus in any of the muscle layers.
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PMID:NADPH-diaphorase-positive nerve fibers in smooth muscle layers of opossum esophagus: gradients in density. 754 93

The distribution of nitric oxide synthase-immunoreactive (NOS-IR) axons and their relationship to structures immunoreactive to vasoactive intestinal polypeptide (VIP), substance P (SP) and tyrosine hydroxylase (TH) were studied by means of the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) technique or double-labelling immunofluorescence in the genital organs of cow and pig. Relevant neurons were also investigated in the pig. NOS-containing neural structures were TH-immunonegative in bovine or porcine genital organs, or in the studied ganglia. In the bovine ovary, NOS-IR nerves were neither VIP-IR nor SP-IR, whereas in the pig, most NOS-containing axons were also VIP-IR. The oviduct was supplied by single NOS/VIP- or NOS/SP-containing nerves, whereas in the uterus, NOS-IR axons were moderate in number, often being immunoreactive for VIP or SP. Numerous NOS/VIP-IR and NOS/SP-IR nerves were found in the vagina of both species. In all tissues studied, NOS-IR axons were mainly related to vascular smooth muscle. Most of the neurons of the paracervical ganglia and some neurons in dorsal root ganglia exhibited strong NOS activity. Only single neurons in sympathetic ganglia were NADPH-d-positive. Most nitrergic neurons in the autonomic ganglia were VIP-IR but SP-immunonegative. The sensory neurons were mostly NOS/SP-IR, whereas only single neurons co-expressed NOS and VIP immunoreactivity.
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PMID:The distribution and co-localization of immunoreactivity to nitric oxide synthase, vasoactive intestinal polypeptide and substance P within nerve fibres supplying bovine and porcine female genital organs. 755 66

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.
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PMID:Functional role and histological demonstration of nitric-oxide-mediated inhibitory nerves in dog sphincter of Oddi. 857 10

The rat uterus is innervated by sensory and autonomic nerves. Sensory and sympathetic fibers travel in the hypogastric nerves and are associated with the thoracolumbar spinal cord levels T13-L3. The inferior mesenteric ganglion (IMG) contains the somata of sympathetic postganglionic neurons and some of these may project axons to the uterus. Sensory and parasympathetic fibers travel in the pelvic nerve and are associated with the lumbosacral cord levels L6-S1 and pelvic ganglion (PG). We previously reported data concerning the neurochemical anatomy of the PG with regard to the uterine innervation; the present study was undertaken to characterize the neurochemical anatomy of the IMG with regard to it involvement in uterine innervation. A retrograde axonal tracer was used to verify projections of axons of IMG neurons to the uterus. Immunostaining of cryostat sections of the IMG revealed neurons immunoreactive for neuropeptide Y (NPY) and for tyrosine hydroxylase (TH). Immunostaining for the synaptic terminal protein synapsin I (SYN) revealed numerous fine terminals immediately surrounding the principal neurons and in the interneuronal spaces. Varicosities immunoreactive for calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), enkephalin (ENK), substance P (SP) and galanin (GAL) appear to be associated with principal neurons. Additional varicosities stained for nicotinamide adenine dinucleotide phosphate (reduced)-diaphorase (NADPH-d) and nitric oxide synthase (NOS), thus indicating sites of neuronal nitric oxide synthesis. This study revealed that the IMG contains uterine-related neurons and that some of the retrogradely labeled uterine-related neurons contain NPY, TH or both NPY/TH. In addition, uterine-related neurons received abundant afferent inputs indicated by SYN-immunoreactive (-ir) terminals and some of these varicosities labeled for GAL, CGRP, VIP, ENK, or NADPH-d/NOS.
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PMID:Identification of uterine-related sympathetic neurons in the rat inferior mesenteric ganglion: neurotransmitter content and afferent input. 881 65

While the crucial role of neurally produced nitric oxide in mediating penile erection is well established, the understanding of the peripheral neuroanatomy of the nitric oxide-ergic pathways is still incomplete. This study was designed to elucidate further the distribution of nitric oxide synthase, and its relation to the distribution of neuropeptides and tyrosine hydroxylase in all penis-projecting neural pathways. A triple-labelling technique was employed, with the retrograde tracer Fluoro Gold combined with neuropeptide immunohistochemistry and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry, a marker of nitric oxide synthase. The presence within the penis of scattered nerve cell bodies exhibiting NADPH-diaphorase activity was revealed. Most (76%) of the penis-projecting neurons in the major pelvic ganglion exhibited NADPH-diaphorase activity and immunoreactivity to vasoactive intestinal peptide, while none of them contained tyrosine hydroxylase. Sympathetic paravertebral postganglionic neurons, in turn, contained tyrosine hydroxylase, but did not exhibit NADPH-diaphorase activity. In the afferent, sensory neurons projecting to the penis from the dorsal root ganglia, NADPH-diaphorase activity coexisted with immunoreactivity to both substance P (8%) and calcitonin gene-related peptide (26%). Preganglionic neurons originating in the spinal cord intermediolateral column at the thoracolumbar level T11-L3 terminated, not only in the major pelvic ganglion, but also within the penis. The majority (81%) of the penis-projecting neurons exhibited NADPH-diaphorase activity. The results indicate that the rat penis receives several different nitric oxide-ergic neural projections. It is therefore possible that nitric oxide affects penile erection at several neuronal levels.
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PMID:Nitric oxide-synthesizing neurons originating at several different levels innervate rat penis. 895 82

The distribution of nitrergic neurons in the pancreas of the newborn guinea pig was first investigated, using nitric oxide synthase (NOS) immunofluorescence and nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d) histochemistry. There was total colocalization of NOS and NADPH-d in the pancreatic ganglion cells. NADPH-d was then used as a marker for NOS. In the whole mount preparation of the pancreas, most of the nitrergic neurons were located in the head and the body region, along the branches of pancreatic blood vessels. Some were also associated with the main pancreatic duct, islets of Langerhans and pancreatic acini. To investigate whether NADPH-d stained cells were neurons and whether NADPH-d was colocalized with various neuropeptides and dopamine-beta-hydroxylase (D beta H), an enzyme involved in the synthesis of noradrenaline, antibodies against neuron specific enolase (NSE), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY). D beta H, substance P (SP), calcitonin gene-related peptide (CGRP) and bombesin (BOM) were used. Of all NSE positive ganglion cells, 76.8% were NADPH-d positive. NOS, VIP, NPY and D beta H immunoreactivities were found in both the neuronal cell bodies and nerve fibres in the pancreas while SP, CGRP and BOM immunoreactivities were detected only in the nerve fibres. SP-, CGRP- and BOM-containing nerves were in close contact with both NADPH-d positive as well as NADPH-d negative neurons. The percentages of NADPH-d/VIP, NADPH-d/NPY, NADPH-d/D beta H neurons in the total number of pancreatic neurons were 67.4%, 53.5%, 21.5% respectively. With double labelling in adjacent sections three subpopulations of pancreatic ganglion cells were demonstrated: NADPH-d/VIP/NPY, NADPH-d/VIP/D beta H and NADPH-d/NPY/D beta H.
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PMID:Nitrergic neurons in the pancreas of newborn guinea pig: their distribution and colocalization with various neuropeptides and dopamine-beta-hydroxylase. 898 82

A primary neurogenic component is often being postulated to be responsible for unfavourable postoperative results of bladder growth and continence in the exstrophy-epispadias complex. On the other hand, we have seen favourable clinical situations and urodynamic follow-up after primary reconstruction employing the 'Erlangen technique' without evidence of primary dysinnervation. Since there are only few data available on this issue, we decided to apply immunocytochemistry and histochemistry for neuronal markers as a further step to elucidate this problem. Transmural biopsies were obtained during reconstructive surgery from the bladder dome and trigone of 22 children between September 1994 and June 1995. Indirect immunocytochemistry for vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), substance P (SP) calcitonin gene-related product (CGRP) and protein gene product (PGP) 9.5, a universal marker for neuronal tissue and histochemistry for nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd), was performed on 14-micron cryostat sections. During the same period of time, control biopsies from 6 healthy bladders of an age-compatible group were subjected to the same examination. In addition, 19 patients were examined urodynamically after reconstruction in order to compare postoperative bladder function with the preexisting innervation pattern. No evidence of dysinnervation was found either morphologically or urodynamically in cases of isolated epispadias and classical exstrophy. Cases of exstrophies after failed reconstruction had muscular innervation deficiencies but increased sub and intraepithelial innervation. This group, according to morphological changes, also demonstrated bladder wall instability, decreased bladder compliance and absent detrusor contractions during micturition. All cloacal exstrophies had an extremely uneven innervation pattern with noticeable calibre differences of nerve fibres and bundles with simultaneously increased innervation density. Functionally these bladders were marked by small capacity and decreased compliance and absent detrusor function. All exstrophies in conjunction with an anal atresia or with a caudal regression syndrome (so-called 'transition forms') had a nearly universal pathological innervation pattern, compatible with cloacal exstrophies and had equally unfavourable functional findings. Cloacal exstrophies and 'transition forms' seemed to have primarily a completely different pattern of innervation when compared to normal bladders. Prognosis of bladder function in these children remains unclear.
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PMID:Comparison of preoperative innervation pattern and postreconstructive urodynamics in the exstrophy-epispadias complex. 931 17


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