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

The aims of the present study were to determine whether nerves that contain nitric oxide synthase (NOS), calcitonin gene-related peptide (CGRP) or substance P (SP) are present in the human vagina and, if so, to determine the pattern of innervation relative to that of other neurotransmitters, particularly vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY). Surgical specimens of vaginal tissue (n = 10) from pre- and postmenopausal women were fixed and processed for immunohistochemistry of peptides and NOS and for histochemistry of NADPH-diaphorase. SP-immunoreactive nerves were very sparse, being absent from 9 of the 10 tissue samples. For other peptides and NOS, the innervation of the deep arteries and veins was greater than that of blood vessels in the propria. Capillaries in the epithelial papillae also appeared to be innervated by nerves containing NOS, CGRP, NPY and VIP. Beneath the epithelium nerve fibres formed a subepithelial plexus; no nerve cell bodies were seen. The relative density of innervation by immunoreactive fibres was PGP-9.5 > NPY > VIP >> NOS > CGRP > SP. These results imply that nerves that utilise nitric oxide or NPY, VIP or CGRP as a neurotransmitter may play a role in controlling blood flow and capillary permeability in the human vagina. The origin and function of all these nerves is discussed.
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PMID:Innervation of vasculature and microvasculature of the human vagina by NOS and neuropeptide-containing nerves. 876 80

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

37 complete frontal and horizontal series of rat brain were studied to compare the distribution of choline acetyltransferase- (ChAT), tyrosine hydroxylase- (TH), substance P- (SP), calbindin D- (Calb) and NADPH-diaphorase (NADPH-d)-positive cells within the cytoarchitectonic borders of the latero-dorsal tegmental nucleus (L-D) and its neighbourhood. We found the same distribution, number and morphology of NADPH-d-positive cells and ChAT-positive cells. Rostrally, there are no borders between NADPH-d-positive cells of L-D and NADPH-d-positive cells of the lateral part of the dorsal raphe nucleus. Only a few TH-positive cells are intermingled with ChAT/NADPH-d-positive cells at the lateral border of L-D. TH-positive cells are larger or the same size as cholinergic neutrons. Locus coeruleus and its rostral part is full of TH-positive cells and their fibres run ventromedially towards L-D. Barrington's nucleus appears in double staining (ChAT and TH or NADPH-d and TH) as an empty area bordered by ChAT- or NADPH-d-positive cells of L-D and TH-positive fibres of the locus coeruleus. Some of these fibres run through the Barrington's nucleus. The shape and size of SP-positive neurons is the same as ChAT- and NADPH-d-positive neurons. SP-positive neurons are sparsely distributed in all parts of L-D, but there are only a few SP-positive cells in its medial part. About 50% of the ChAT- and NADPH-d-positive cells are also SP-positive. Results are expressed by figures in three representative frontal sections and one horizontal section through the dorsal mesopontine tegmentum.
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PMID:The dorsal tegmentum of the pontomesencephalic junction of the rat--immunohistochemistry (choline acetyltransferase, tyrosine hydroxylase, substance P) and NADPH-diaphorase histochemistry in frontal and horizontal sections. 917 35

In this study, enteric nervous system (ENS) of the fetal intestinal grafts was examined histopathologically. Forty-four rat fetal small intestines were transplanted syngenetically into the subcutaneous region of adult rats without vascular anastomosis. Thirty-two grafts survived. They were removed 2, 4, 6, and 8 weeks after transplantation and examined using (1) H&E staining, (2) AChE and NADPH-diaphorase histochemistry, and (3) protein gene product 9.5, S-100 protein, glial fibrillary acidic protein, tyrosine hydroxylase, nerve growth factor receptor, calcitonin gene-related peptide, neuropeptide Y, vasoactive intestinal peptide, somatostatin, and substance P immunohistochemistry. The grafts were compared with the intestines of 2-, 4-, 6- and 8-week-old control rats. ENS of the grafts was different from the controls as follows: (1) tyrosine hydroxylase and neuropeptide Y were markedly reduced but present, suggesting that the extrinsic innervation was present; (2) nitric oxide-producing neurons were well preserved in grafts; (3) hyperganglionosis in the myenteric plexus was seen in 6- and 8-week grafts; (4) AChE activity was increased in the circular muscle and in the lamina propria, (5) S-100 was increased in the lamina propria in 6- and 8-week grafts, (6) calcitonin gene-related peptide was increased in 6- and 8-week grafts, (7) nerve fibers in the muscle layers ran irregularly and disorderly, and (8) hypertrophy of smooth muscle layers. Our data show that although extrinsic as well as intrinsic innervation is present in the fetal intestinal grafts, there is hyperinnervation of the intrinsic nervous system and reduced innervation of the extrinsic ENS. These morphological changes in the ENS of the fetal intestinal grafts may result in motility dysfunction.
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PMID:Morphological changes in the enteric nervous system of the transplanted fetal rat intestine. 920 96

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

The muscle and epithelial tissues of the gallbladder are regulated by a ganglionated plexus that lies within the wall of the organ. Although these ganglia are derived from the same set of precursor neural crest cells that colonize the gut, they exhibit structural, neurochemical and physiological characteristics that are distinct from the myenteric and submucous plexuses of the enteric nervous system. Structurally, the ganglionated plexus of the guinea pig gallbladder is comprised of small clusters of neurons that are located in the outer wall of the organ, between the serosa and underlying smooth muscle. The ganglia are encapsulated by a shell of fibroblasts and a basal lamina, and are devoid of collagen. Gallbladder neurons are rather simple in structure, consisting of a soma, a few short dendritic processes and one or two long axons. Results reported here indicate that all gallbladder neurons are probably cholinergic since they all express immunoreactivity for choline acetyltransferase. The majority of these neurons also express substance P, neuropeptide Y, and somatostatin, and a small remaining population of neurons express vasoactive intestinal peptide (VIP) immunoreactivity and NADPH-diaphorase enzymatic activity. We report here that NADPH-diaphorase activity, nitric oxide synthase immunoreactivity, and VIP immunoreactivity are expressed by the same neurons in the gallbladder. Physiological studies indicate that the ganglia of the gallbladder are the site of action of the following neurohumoral inputs: 1) all neurons receive nicotinic input from vagal preganglionic fibers; 2) norepinephrine released from sympathetic postganglionic fibers acts presynaptically on vagal terminals within gallbladder ganglia to decrease the release of acetylcholine from vagal terminals; 3) substance P and calcitonin gene-related peptide, which are co-expressed in sensory fibers, cause prolonged depolarizations of gallbladder neurons that resemble slow EPSPs; and 4) cholecystokinin (CCK) acts presynaptically within gallbladder ganglia to increase the release of acetylcholine from vagal terminals. Results reported here indicate that hormonal CCK can readily access gallbladder ganglia, since there is no evidence for a blood-ganglionic barrier in the gallbladder. Taken together, these results indicate that gallbladder ganglia are not simple relay stations, but rather sites of complex modulatory interactions that ultimately influence the functions of muscle and epithelial cells in the organ.
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PMID:Innervation of the gallbladder: structure, neurochemical coding, and physiological properties of guinea pig gallbladder ganglia. 932 15

The autonomic nervous system is involved in different functions such as transduction of afferent sensory inputs, trophic actions, modulation of immunologic events and thermoregulation. In the present investigation, we studied the pattern of human autonomic skin innervation with special reference to its relation to blood vessels, hair follicles, sweat glands and sensory receptors. For the first time, two clinically important areas have been compared: the skin of the forearm and of the face. Using indirect immunohistochemistry, we analyzed the distribution of calretinin (CR), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP), neurokinin A (NKA), vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS), tyrosine hydroxylase (TH), histamine, serotonin, enkephalin, and, enzyme histochemically, NADPH-diaphorase (NADPH-d). In the epidermis, we found nerve fibers containing SP, NKA and CGRP. In the dermis, SP-, CR-, VIP-, CGRP- and NKA-positive nerve fibers were detected. Particularly the large nerve fibers contained CR. VIP-positive fibers occurred especially around hair follicles and sweat glands. CGRP-positive nerve fibers were located close to the epidermal basal membrane, in the wall of blood vessels, and to a lesser extent around hair follicles. Immunoreactivity for SP and NKA in the dermis was observed predominantly in the papillary layer near the epidermal basal membrane. All neuropeptides tested in this study were also detected in the nerve fibers of the subcutis. Most of them were CGRP- and VIP-positive. They occurred in association with sweat glands and large arteries. NPY-positive nerve fibers are predominant in the wall of arteries, arterioles and veins. Nerve fibers containing NKA and SP were less common and identified only in the walls of large arteries in deeper dermal layers. In double-staining experiments, the NADPH-d reaction and reactivity to tubulin revealed a partial co-localization in nerve fibers, blood vessel walls, around glands and ganglionic cells. VIP-positive fibers were more common in the face skin than in the forearm. However, in forearm we detected more NPY-, CGRP-, NKA- and SP-positive nerve fibers than in face skin. These findings are important for future studies on skin disorders, such as sensory neuropathies, inflammatory reactions or allergic responses of human skin.
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PMID:Immunohistochemical detection of human skin nerve fibers. 938 13

We investigated the distribution of parasympathetic, sympathetic, and sensory perivascular nerve fibers in rabbit cephalic arteries supplying the brain, exocrine glands, nasal mucosa, masseter muscles, tongue, and skin in the face and also examined cranial autonomic and sensory ganglia. NADPH diaphorase (NADPHd)-positive and vasoactive intestinal peptide-like immunoreactive (VIP-LI) neurons were located in the cranial parasympathetic ganglia. Neuropeptide Y (NPY)-LI neurons occurred mainly, and dopamine beta-hydroxylase (DBH)-LI neurons occurred exclusively, in the superior cervical (sympathetic) ganglion. Substance P (SP)-LI and calcitonin gene-related peptide (CGRP)-LI neurons occurred only in the trigeminal (sensory) ganglion. Therefore, it was assumed that NADPHd-positive and VIP-LI perivascular nerve fibers in cephalic arteries were parasympathetic, all DBH-LI and most NPY-LI fibers were sympathetic, and SP-LI and CGRP-LI fibers were sensory in nature. In the cerebral arteries, NADPHd-positive and VIP-LI varicose fibers were more numerous in the rostral than in the caudal half of the Circle of Willis. In the extracranial arteries, NADPHd-positive and VIP-LI fibers were most abundant in the lingual, lacrimal, and supraorbital arteries; sparse in the parotid and submandibular arteries; and absent in the ear artery. There was an obvious proximal-to-distal density gradient along individual cephalic arterial trees. In contrast, DBH-LI, NPY-LI, SP-LI, and CGRP-LI varicose nerve fibers were similar in density in all cephalic arteries and their branches. These neuroanatomical findings suggest that differential parasympathetic innervation in cephalic arteries may play a role in the partitioning of blood flow between different cephalic tissues.
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PMID:Parasympathetic innervation of cephalic arteries in rabbits: comparison with sympathetic and sensory innervation. 941 8


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