UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ganglion cells and topographically related nerves in the vallate papilla/von Ebner gland complex were investigated in rat tongue by cytochemical, immunocytochemical, and ultrastructural methods to evaluate the possible presence of different neuronal subpopulations. Immunostaining for neurofilaments and protein gene product 9.5 revealed ganglionic cell bodies and nerve fibers. A large part of the neurons were positive at immunostaining for neuronal nitric oxide synthase (NOS), vesicular acetylcholine transporter (VAChT), or vasoactive intestinal peptide (VIP). A small subset of nerve fibers revealed immunoreactivity for cholecystokinin. Axons traveling under the lingual epithelium were evidenced by their content of calcitonin gene-related peptide (CGRP) or substance P (SP). Cell bodies positive for SP or CGRP were not detected. Using methods of co-localization, three different neuronal classes were detected. The main population was composed of AChE/NADPH-diaphorase (NADPHd)-positive cells. Small groups of acetylcholine esterase (AChE)-positive/NADPHd-negative cells were visible. Isolated neurons were AChE-negative/NADPHd-positive. The results of co-localization experiments for VAChT/NOS were consistent with those obtained by cytochemical co-localization of AChE and NADPHd. Experiments of co-localization for peptidergic and nitrergic structures revealed CGRP- and SP-immunoreactive fibers in the vallate papilla/von Ebner gland ganglion. In conclusion, the results demonstrated in the VP/VEG complex peptidergic, cholinergic, and nitrergic neurons. The presence of different neuronal subclasses suggests that a certain degree of functional specialization may exist.
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PMID:Ganglion cells and topographically related nerves in the vallate papilla/von Ebner gland complex. 1196 82

Nerve fibres play an important role in the regulation of gastric emptying. The aims of this study were to clarify the distribution, projections and origin of neuronal type nitric oxide synthase (NOS)-, tyrosine hydroxylase (TH)-, vesicular acetylcholine transporter (VAchT)- and peptide-containing nerve fibres of the rat pyloric sphincter. Extrinsic and local denervations of the sphincter were performed in order to reveal the origin and projections of the various nerve fibre populations. Pylorus from control and denervated animals were processed for the immunocytochemical demonstration of cholecystokinin (CCK), enkephalin, gastrin-releasing peptide (GRP), somatostatin, calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), pituitary adenylate cyclase-activating peptide (PACAP), substance P (SP), vasoactive intestinal peptide (VIP), galanin, NOS, VAchT and TH. VAchT, TH, nNOS, and all of the peptides investigated were found in nerve fibres innervating the pyloric sphincter, and coexistence of several putative neurotransmitters were revealed. Extrinsic denervation caused a total loss of NPY/TH-, SP/CGRP- and SP/CGRP/VIP/NOS/PACAP-containing nerve fibres. Local denervation immediately proximal to the sphincter markedly reduced the numbers of VIP/NOS/galanin- and VIP/NOS/galanin/PACAP +/- NPY-containing fibres within the sphincter suggesting an origin of these fibres in myenteric ganglia in the antral region; denervation at the level of the oxyntic-pyloric border had no effect. Local denervation immediately distal to the sphincter caused a marked decrease in VAchT-, SP/enkephalin-, enkephalin-, somatostatin-, CCK- and GRP-containing fibres within the sphincter suggesting that these emanate from the duodenum. The latter procedure also reduced the number of SP/CGRP-containing fibres of extrinsic origin within the pyloric sphincter.
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PMID:Origins and projections of nerve fibres in rat pyloric sphincter. 1213 47

The urine storage ability of the urinary bladder is markedly impaired following inflammation of the urinary bladder and spinal cord injury because of a hyperexcitability of micturition reflexes. Using two rat models of inflammation-induced bladder overactivity and detrusor hyper-reflexia following spinal cord injury we investigated changes in the neuronal pathways to the urinary bladder which may underlie the development of this instability. Our results suggest that among the factors involved in inflammation-induced bladder instability are significant changes in the expression of the neuropeptides substance P, calcitonin gene-related peptide and galanin at the primary afferent level, as well as of the enzyme neuronal nitric oxide synthase (nNOS) at the afferent and postganglionic efferent level. In the lumbar and sacral spinal cord nNOS-immunoreactivity was depleted from dorsal horn neurones in both cystitis and spinal cord injured rats and from preganglionic parasympathetic neurones after spinal cord injury. Distension of the bladder in chronically spinalized rats elicited c-Fos expression in a significantly greater number of neurones throughout the lumbar and sacral segments than in rats with an intact neuraxis. Thus, under pathological conditions rather complicated changes in the synthesis of neuropeptides and nNOS occur at the primary afferent, spinal cord and postganglionic efferent level that together control the activity of the urinary bladder. Further mechanisms like unmasking of silent synapses and axonal sprouting in the spinal cord might further contribute to an increase in activity in micturition reflex pathways. Local cooling of the dorsal spinal cord at the level L6/S1 with temperatures between 14 and 20 degrees C proved a simple technique to control the unstable bladder and restore continence in both inflammation-induced detrusor overactivity and detrusor hyperreflexia following spinal cord injury. The effects of cooling are probably the result of a blockade of synaptic transmission within the dorsal cord which eliminates neuronal overactivity. Thus, local spinal cord cooling could offer a new method to treat bladder instability and reflex incontinence.
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PMID:Mechanisms underlying the pathogenesis of urinary bladder instability - new perspectives for the treatment of reflex incontinence. 1267 Dec 55

Although the rabbit brain, in particular the basal forebrain cholinergic system, has become a common model for neuropathological changes associated with Alzheimer's disease, detailed neuroanatomical studies on the morphological organization of basal forebrain cholinergic nuclei and on their output pathways are still awaited. Therefore, we performed quantitative choline acetyltransferase (ChAT) immunocytochemistry to localize major cholinergic nuclei and to determine the number of respective cholinergic neurons in the rabbit forebrain. The density of ChAT-immunoreactive terminals in layer V of distinct neocortical territories and in hippocampal subfields was also measured. Another cholinergic marker, the low-affinity neurotrophin receptor (p75(NTR)), was also employed to identify subsets of cholinergic neurons. Double-immunofluorescence labeling of ChAT and p75(NTR), calbindin D-28k (CB), parvalbumin, calretinin, neuronal nitric oxide synthase (nNOS), tyrosine hydroxylase, or substance P was used to elucidate the neuroanatomical borders of cholinergic nuclei and to analyze the neurochemical complexity of cholinergic cell populations. Cholinergic projection neurons with heterogeneous densities were found in the medial septum, vertical and horizontal diagonal bands of Broca, ventral pallidum, and magnocellular nucleus basalis (MBN)/substantia innominata (SI) complex; cholinergic interneurons were observed in the caudate nucleus, putamen, accumbens nucleus, and olfactory tubercule, whereas the globus pallidus was devoid of cholinergic nerve cells. Cholinergic interneurons were frequently present in the hippocampus and to a lesser extent in cerebral cortex. Cholinergic projection neurons, except those localized in SI, abundantly expressed p75(NTR), and a subset of cholinergic neurons in posterior MBN was immunoreactive for CB and nNOS. A strict laminar distribution pattern of cholinergic terminals was recorded both in the cerebral cortex and in CA1-CA3 and dentate gyrus of the hippocampus. In summary, the structural organization and chemoarchitecture of rabbit basal forebrain may be considered as a transition between that of rodents and that of primates.
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PMID:Rabbit forebrain cholinergic system: morphological characterization of nuclei and distribution of cholinergic terminals in the cerebral cortex and hippocampus. 1271 17

Mechanical activation of the mucosal lining of the colon by brush stroking elicits an intestinal neural reflex and an increase in short circuit current (Isc) indicative of electrogenic chloride ion transport. We tested whether endogenous nucleotides are physiologic regulators of mucosal reflexes that control ion transport. The brush stroking-evoked Isc response in mucosa and submucosa preparations (M-SMP) of rat colon was reduced by the P2Y1 receptor (R) antagonist 2'deoxy-N6-methyl adenosine 3',5'-diphosphate diammonium salt (MRS 2179) and further blocked by tetrodotoxin (TTX). M-SMP Isc responses to serosal application of the P2Y1 R agonist 2-methylthioadenosine-diphosphate (2MeSADP) or the P2Y2/P2Y4 R agonist 5'uridine-triphosphate (UTP) were reduced but not abolished by TTX. The potency profile of nucleotides for increasing Isc was 5'adenosine-triphosphate (ATP; effective concentration at half maximal response [EC50] 0.65 x 10(4) M) congruent with UTP (EC50 1.0 x 10(-4) M) congruent with 2MeSADP (EC50 = 1.60 x 10(-4) M). Mucosal touch and distention-induced Ca2+ transients in submucous neurons were reduced by apyrase and prevented by blocking the P2Y1 R with MRS 2179 and TTX; denervation of the mucosa. It did not occur by touching a ganglion directly. 2MeSADP Ca2+ responses occurred in subsets of neurons with or without substance P (SP) responses. The potency profile of nucleotides on the neural Ca2+ response was 2MeSADP (5 x 10(-7) M) > UTP (6 x 10(-6) M) > ATP (9 x 10(-5) M). The expression of P2Y R immunoreactivity (ir) in nerve cell bodies was in the order of P2Y1 R > P2Y4 R >> P2Y2 R. P2Y1R ir occurred in the cell somas of more than 90% of neuronal nitric oxide synthase, vasoactive intestinal peptide (VIP), calretinin, or neuropeptide Y (NPY)-ir neurons, 78% of somatostatin neurons, but not in calbindin or SP neurons. P2Y2 R ir was expressed in a minority of SP, VIP, NPY, vesicular acetylcholine transporter, and calcitonin gene-related peptide-ir varicose fibers (5-20%) and those surrounding calbindin (5-20%) neurons. P2Y4 ir occurred mainly in the cell somas of 93% of NPY neurons. Reverse transcriptase polymerase chain reaction of the submucosa demonstrated mRNA for P2Y1R, P2Y2, P2Y4, P2Y6, and P2Y12 Rs. Expression of P2Y1, P2Y2, and P2Y4 protein was confirmed by western blots. In conclusion, endogenous nucleotides acting at P2YRs transduce mechanically evoked reflex chloride ion transport in rat distal colon. Nucleotides evoke reflexes by acting primarily at postsynaptic P2Y1 Rs and P2Y4 R on VIP+/NPY+ secretomotor neurons, at P2Y2 Rs on no more than 2% of VIP+ secretomotor neurons, and 2Y2 Rs mainly of extrinsic varicose fibers surrounding putative intrinsic primary afferent and secretomotor neurons. During mucosal mechanical reflexes, it is postulated that P2Y1 R, P2Y2 R, and P2Y4 R are activated by endogenous ATP, UTP, and 5'uridine-diphosphate.
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PMID:Mechanically evoked reflex electrogenic chloride secretion in rat distal colon is triggered by endogenous nucleotides acting at P2Y1, P2Y2, and P2Y4 receptors. 1468 71

The expression pattern of proinflammatory cytokines, neuronal nitric oxide synthase (nNOS), substance P (SP) and calcitonin gene related peptide (CGRP) in the spinal cord and the bladder in response to permanent middle cerebral artery occlusion (MCAO) was investigated. In this connection, the gene expression of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and interleukin-6 in the lumbosacral spinal cord and the bladder as determined by real-time polymerase chain reaction was upregulated. In the spinal cord, the immunoreactivity of TNF-alpha and IL-1beta was mainly localized in the ventral horn motoneurons contralateral to MCAO. In the bladder, TNF-alpha was mainly expressed in the inflammatory cells. The expression of nNOS immunoreactivity as well as nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining in the spinal cord and bladder was also markedly increased in response to MCAO. Furthermore, the temporal and spatial expression of nNOS paralleled that of TNF-alpha and IL-1beta in the spinal cord. On the other hand, there was no noticeable change in gene expression and immunoreactivity of SP and CGRP. The present results have shown that cytokines and nNOS expression are elevated in areas far removed from the primary site of ischemic infarct, namely, the lumbosacral spinal cord and bladder. This together with some neuronal deaths maybe linked to the dysfunction of the latter in a clinical stroke. On the other hand, the apparent lack of SP and CGRP changes following MCAO suggests that the two neurotransmitters are not directly involved.
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PMID:Permanent occlusion of the middle cerebral artery upregulates expression of cytokines and neuronal nitric oxide synthase in the spinal cord and urinary bladder in the adult rat. 1512 Aug 43

Intraganglionic laminar endings (IGLEs) represent the only vagal mechanosensory terminals in the tunica muscularis of the esophagus and may be involved in local reflex control. We recently detected extensive though not complete colocalization of the vesicular glutamate transporter 2 (VGLUT2) with markers for IGLEs. To elucidate this colocalization mismatch, this study aimed at identifying markers for nitrergic, cholinergic, peptidergic, and adrenergic neurons and glial cells, which may colocalize with VGLUT2 outside of IGLEs. Confocal imaging revealed, besides substantial colocalization of VGLUT2 and substance P (SP), no other significant colocalizations of VGLUT2 and immunoreactivity for any of these markers within the same varicosities. However, we found close contacts of VGLUT2-positive structures to vesicular acetylcholine transporter, choline acetyltransferase, neuronal nitric oxide synthase, galanin, neuropeptide Y, and vasoactive intestinal peptide immunoreactive cell bodies and varicosities, as well as to glial cells. Neuronal perikarya were never positive for VGLUT2. Thus, VGLUT2 was almost exclusively found in IGLEs and may serve as a specific marker for them. In addition, many IGLEs also contained SP. The close contacts established by IGLEs to myenteric cell bodies, dendrites, and varicose fibers suggest that IGLEs modulate various types of enteric neurons and vice versa.
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PMID:Intraganglionic laminar endings and their relationships with neuronal and glial structures of myenteric ganglia in the esophagus of rat and mouse. 1537 79

The role of neural elements in regulating blood flow through the hepatic sinusoids, solute exchange, and parenchymal function is incompletely understood. This is due in part to limited investigation in only a few species whose hepatic innervation may differ significantly from humans. For example, most experimental studies have used rats and mice having livers with little or no intralobular innervation. In contrast, most other mammals, including humans, have aminergic and peptidergic nerves extending from perivascular plexus in the portal space into the lobule, where they course in Disse's space in close relationship to stellate cells (fat storing cells of Ito) and hepatic parenchymal cells. While these fibers extend throughout the lobule, they predominate in the periportal region. Cholinergic innervation, however, appears to be restricted to structures in the portal space and immediately adjacent hepatic parenchymal cells. Neuropeptides have been colocalized with neurotransmitters in both adrenergic and cholinergic nerves. Neuropeptide Y (NPY) has been colocalized in aminergic nerves supplying all segments of the hepatic-portal venous and the hepatic arterial and biliary systems. Nerve fibers immunoreactive for substance P and somatostatin follow a similar distribution. Intralobular distribution of all of these nerve fibers is species-dependent and similar to that reported for aminergic fibers. Vasoactive intestinal peptide and calcitonin gene-related peptide (CGRP) are reported to coexist in cholinergic and sensory afferent nerves innervating portal veins and hepatic arteries and their branches, but not the other vascular segments or the bile ducts. Nitrergic nerves immunoreactive for neuronal nitric oxide (nNOS) are located in the portal tract where nNOS colocalizes with both NPY- and CGRP-containing fibers. In summary, the liver is innervated by aminergic, cholinergic, peptidergic, and nitrergic nerves. While innervation of structures in the portal tract is relatively similar between species, the extent and distribution of intralobular innervation are highly variable as well as species-dependent and may be inversely related to the density of gap junctions between contiguous hepatic parenchymal cells.
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PMID:Anatomy of efferent hepatic nerves. 1538 19

The hph-1 mice have defective tetrahydrobiopterin biosynthesis and share many neurochemical similarities with l-dopa-responsive dystonia (DRD) in humans. In both, there are deficiencies in GTP cyclohydrolase I and low brain levels of dopamine (DA). Striatal tyrosine hydroxylase (TH) levels are decreased while the number of DA neurones in substantia nigra (SN) appears normal. The hph-1 mouse is therefore a useful model in which to investigate the biochemical mechanisms underlying dystonia in DRD. In the present study, the density of striatal DA terminals and DA receptors and the expression of D-1, D-2, and D-3 receptors, preproenkephalin (PPE-A), preprotachykinin (PPT), and nitric oxide synthase (NOS) mRNAs in the striatum and nucleus accumbens and nigral TH mRNA expression were examined. Striatal DA terminal density as judged by specific [3H]mazindol binding was not altered while the levels of TH mRNA were elevated in the SN of hph-1 mice compared to control (C57BL) mice. Total and subregional analysis of the striatum and nucleus accumbens showed that D-2 receptor ([3H]spiperone) binding density was increased while D-1 receptor ([3H]SCH 23390) and D-3 receptor ([3H]7-OH-DPAT) binding density was not altered. In the striatum and nucleus accumbens, expression of PPT mRNA was elevated but PPE-A mRNA, D-1, D-2 receptor, and nNOS mRNA were not changed in hph-1 mice compared to controls. These findings suggest that an imbalance between the direct strionigral and indirect striopallidal output pathways may be relevant to the genesis of DRD. However, the pattern of changes observed is not that expected as a result of striatal dopamine deficiency and suggests that other effects of GTP cyclohydrolase I deficiency may be involved.
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PMID:Alterations in expression of dopamine receptors and neuropeptides in the striatum of GTP cyclohydrolase-deficient mice. 1553 Aug 90

Intestinal ischemia impairs gastrointestinal motility. The aims of this study were to investigate the effect of intestinal ischemia on gastrointestinal transit and on the expression of enteric transmitters in the rat, and whether the glutamate N-methyl-d-aspartate receptors influence these effects. Ischemia (1 h), induced by occluding the superior mesenteric artery, was followed by 0 or 24 h of reperfusion. Normal and sham-operated rats served as controls. Serosal blood flow was measured with laser Doppler flow meter. Gastrointestinal transit was measured as time of appearance of a marker in fecal pellets. Immunohistochemistry was used to evaluate the number of neurons immunoreactive for neuronal nitric oxide synthase (NOS) or vasoactive intestinal polypeptide and the density of substance P immunoreactive fibers in the myenteric plexus. The N-methyl-d-aspartate receptors antagonist, (+)-5-methyl-10,11-dihydro-5HT-[a,b] cyclohepten-5,10-imine (MK-801) (1 mg/kg i.v.) or the NOS inhibitor, N-nitro-l-arginine (10 mg/kg i.v.) was administered prior to ischemia. Serosal blood flow was decreased by 70% during ischemia, but it was not altered in sham-operated rats. Gastrointestinal transit was significantly prolonged in ischemic/reperfused rats compared with controls. There was a significant increase in the number of vasoactive intestinal polypeptide and neuronal nitric oxide synthase immunoreactive neurons, and a marked decrease of substance P immunoreactive fibers in ischemia followed by 24 h of reperfusion animals compared with controls. These alterations were not observed in ischemia without reperfusion. A significant delay of gastrointestinal transit and increase of vasoactive intestinal polypeptide neurons were also observed in sham-operated rats. The changes in transmitter expression and gastrointestinal transit in ischemic/reperfused rats were prevented by pre-treatment with the NOS inhibitor, N-nitro-l-arginine or the N-methyl-d-aspartate receptors antagonist, MK-801. This study suggests an involvement of the glutamatergic system and its interaction with nitric oxide in intestinal ischemia/reperfusion. Ischemia/reperfusion might induce local release of glutamate that activates N-methyl-d-aspartate receptors leading to increased production of nitric oxide and adaptive changes in enteric transmitters that might contribute to gastrointestinal dysmotility.
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PMID:Effect of N-methyl-d-aspartate receptor blockade on neuronal plasticity and gastrointestinal transit delay induced by ischemia/reperfusion in rats. 1593 44

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