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)

Triple label immunohistochemistry was used to study the coexistence of the catecholamine-synthesising enzymes dopamine beta-hydroxylase (DBH) and tyrosine hydroxylase (TH) and several neuropeptides including neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP), somatostatin (SOM) and galanin (GAL) as well as nitric oxide synthase (NOS) in developing pelvic paraganglion cells in a series of human male fetal, neonatal and infant specimens ranging in age from 13 wk of gestation to 3 y postnatal. 13-20 wk old fetal specimens possessed large clusters of paraganglion cells lying lateral to the urinary bladder and prostate gland which were intensely DBH-immunoreactive (-IR) but lacked TH, NOS and the neuropeptides investigated. With increasing fetal age small clusters of paraganglion cells were observed in the muscle coat of the urinary bladder. At 23 wk of gestation occasional paraganglion cells were NOS or NPY-IR while at 26 wk of gestation the majority of paraganglion cells were TH-IR and a few were SOM or GAL-IR. Some postnatal paraganglia within the bladder musculature contained cells which were all VIP, SP or CGRP-IR while others displayed coexistence of NOS and NPY, SP and CGRP, or NPY and VIP. The presence of NOS in certain paraganglion cells indicates their capacity to generate nitric oxide (NO). These results show that human paraganglion cells develop different phenotypes possibly dependent upon their location within the bladder wall. A delicate plexus of branching varicose nerves was observed in the fetal paraganglia which increased in density with increasing gestational age. The majority of these nerves were VIP-IR while others were CGRP, SP, NPY, NOS or GAL-IR. The presence of nerve terminals adjacent to the paraganglion cells implies a neural influence on the functional activity of the paraganglia. Some paraganglia in the late fetal and early postnatal specimens contained Timofeew's sensory corpuscles, resembling pacinian corpuscles in their morphology. The central nerve fibre of these corpuscles displayed immunoreactivity for SP, CGRP and NOS, the latter indicating a possible role for NO in afferent transmission from the urinary bladder. In addition, a few corpuscles were penetrated by a noradrenergic nerve fibre immunoreactive for NPY and TH, which may have a modulatory role on the sensory receptor.
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PMID:Immunohistochemical characteristics of human paraganglion cells and sensory corpuscles associated with the urinary bladder. A developmental study in the male fetus, neonate and infant. 968 6

Characteristics of the pulpal innervation in teeth obtained from a 4-year-old Asian boy with hereditary sensory and autonomic neuropathy, type II (HSAN) were investigated. Four minimally carious primary teeth were split longitudinally and prepared for either fluorescent immunocytochemistry or electron microscopy. The occurrence and distribution of specific neuropeptides were determined by the use of antisera to calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP). The overall innervation of the pulps was visualized using antiserum to protein gene product 9.5; an antiserum to dopamine beta-hydroxylase was used to identify postganglionic sympathetic fibres. Pulpal innervation in HSAN was notably different from that of normal teeth: in comparison with the controls, HSAN teeth had an overall marked reduction in pulpal innervation with an absence of large nerve bundles and the subodontoblastic plexus. CGRP- and SP-immunoreactivity was absent in HSAN specimens and VIP-immunoreactivity was reduced. However, NPY-immunoreactivity appeared to be increased within certain regions of the pulp/dentine complex. In addition, there was evidence of NPY-immunoreactive fibres extending into dentine, a feature not seen in the controls. Electron microscopy revealed an absence of myelinated nerve fibres and a paucity of unmyelinated fibres. CGRP and SP have a well-established role in nociceptive processing and their absence in the HSAN teeth would seem to correspond with the clinical presentation of marked peripheral sensory deficit, characteristic of this condition. An up-regulation of NPY-immunoreactivity has previously been reported in animal teeth following nerve injury and a similar mechanism may have stimulated increased NPY expression in HSAN teeth, but the functional significance of its presence within dentinal nerves is not known.
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PMID:Immunocytochemical and electron-microscopic features of tooth pulp innervation in hereditary sensory and autonomic neuropathy. 971 82

The effect of sensory and sympathetic denervation on the localization and distribution of nerve fibers immunoreactive (IR) to calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), and dopamine beta-hydroxylase (DBH) was studied in the dental pulp, periodontal ligament (PDL), and gingiva in ferrets. Unilateral axotomy was performed by resection of the inferior alveolar nerve (IAN) 10 days before the experiment (Group 1); sympathectomy, by unilateral removal of the cervical ganglion 5 days before the experiments (Group 2). Immunohistochemistry was performed on free-floating sections by the avidin-biotin-peroxidase technique. A considerably higher density of sensory fibers IR to CGRP and SP was found in the dental pulp than in PDL and gingiva. The majority of pulpal fibers were located in the walls of blood vessels. A subodontoblastic network of fibers IR to CGRP and SP was lacking in incisors and canines and was found only in the coronal pulp in premolars and molars. Sympathetic fibers were sparsely distributed in the pulp, and they were mainly confined to large vessels running centrally in the root pulp as well as the larger vessels in apical PDL and alveolar bone. Gingiva was well supplied with CGRP- and SP-IR nerves, and some NPY and DBH fibers were located in association with larger vessels. Round cell-like structures within the basal part of the epithelium were CGRP-IR. Axotomy induced a complete loss of CGRP- and SP-IR fibers in the anterior part of the jaws, whereas sympathectomy caused a reduction, but not a total loss, of NPY- and DBH-IR nerves. It is concluded that, except for some distributional differences, the oral tissues in the ferret have an abundant sensory innervation similar to that found in other species.
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PMID:Nerve fibers immunoreactive to calcitonin gene-related peptide, substance P, neuropeptide Y, and dopamine beta-hydroxylase in innervated and denervated oral tissues in ferrets. 976 14

Stimulation of extrinsic nerves markedly alters pancreatic endocrine and exocrine secretion, yet little is known of the neurochemical organization and physiologic roles of specific neural pathways within the pancreas. Here we report histochemical staining for acetylcholinesterase (AChE), NADPH-diaphorase (NADPH-d), nitric oxide synthase (NOS), and several neuropeptides to identify the neurotransmitter content of rabbit pancreatic nerves. An extensive network of AChE-positive nerve fibers was found throughout the islets, acini, ducts, ganglia, and blood vessels. All pancreatic neurons were AChE positive, two thirds were NADPH-d positive, and many were NOS positive. Ganglia in the head/neck region were connected to the duodenal myenteric plexus by AChE- and NADPH-d-positive fibers, and NADPH-d-positive pancreatic neurons appeared to send processes toward both the duodenum and pancreas. Many pancreatic neurons were vasoactive intestinal peptide (VIP) positive, and VIP nerve terminals were abundant in ganglia, acini, islets, and ducts. Pituitary adenylate cyclase-activating peptide (PACAP-38)-positive fibers also were observed within acini and passing through ganglia. Substance P (SP)-, calcitonin gene-related peptide (CGRP)-, and dopamine beta-hydroxylase (DBH)-positive fibers were abundant along blood vessels and ducts, and varicose fibers were observed in pancreatic ganglia. Fine galanin-positive fibers were also occasionally observed running with blood vessels and through ganglia. Thus the rabbit pancreas receives a dense, diverse innervation by cholinergic, adrenergic, and peptidergic nerves and cholinergic pancreatic neurons, most also containing VIP or NOS or both, appear to innervate both endocrine and exocrine tissue, and may mediate local communication between the duodenum and pancreas.
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PMID:Morphology and histochemistry of the rabbit pancreatic innervation. 988 61

After spinal cord injury, abnormal responses of spinal cord neurons to sensory input lead to conditions such as autonomic dysreflexia, urinary bladder dyssynergia, muscle spasticity and chronic pain syndromes. These responses suggest that the spinal cord undergoes marked reorganization after an injury. In previous studies, we demonstrated changes in individual patterns of immunoreactivity for growth-associated protein-43, dopamine beta-hydroxylase and substance P that suggest growth and/or changes in expression of neurotransmitter enzymes and peptides in the cord caudal to a transection injury. In the present study we determined whether (i) growth-associated protein-43 and dopamine beta-hydroxylase or substance P were co-expressed in the same neurons prior to cord injury, and (ii) these patterns of expression changed after injury. A change in co-localization patterns caudal to an injury would suggest diversity in responses of different populations of spinal neurons. We used double-labelling immunocytochemistry to determine whether either dopamine beta-hydroxylase or substance P was co-localized with growth-associated protein-43 in control rats and in rats one, two or six weeks after spinal cord transection. We focused on the intermediate gray matter, especially the sympathetic intermediolateral cell column. In control rats, fibres travelling in a stereotyped ladder-like pattern in the thoracic gray matter contained growth-associated protein-43 co-localized with dopamine beta-hydroxylase or substance P. In spinal rats, such co-localization was also observed in spinal cord segments rostral to the cord transection. In contrast, caudal to the transection, substance P and growth-associated protein-43 were found in separate reticular networks. Immunoreactivity for dopamine beta-hydroxylase disappeared in fibres during this time, but was clearly present in somata. Immunoreactivity for growth-associated protein-43 was also found in somata, but never co-localized with that for dopamine beta-hydroxylase. These observations demonstrated co-localization of growth-associated protein-43 with dopamine beta-hydroxylase and substance P in descending spinal cord pathways. Caudal to a cord transection, this co-localization was no longer found, although each substance was present either in an abundant neural network or in somata. One population of spinal neurons responded to cord injury by expressing the growth-associated protein, whereas two others changed in the intensity of their expression of neurotransmitter peptides or enzymes or in the abundance of fibres expressing them. Thus, three populations of spinal neurons had distinct responses to cord injury, two of them increasing their potential input to spinal sensory, sympathetic or motor neurons. Such responses would enhance transmission through spinal pathways after cord injury.
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PMID:Co-localization of substance P and dopamine beta-hydroxylase with growth-associated protein-43 is lost caudal to a spinal cord transection. 1033 36

The autonomic innervation of the mammalian respiratory system is complex, and involves a wide variety of peptide and non-peptide neurotransmitters which will have an important role in normal laryngeal function and the response to disease. This innervation has been partially described in the horse airway and lung, but there is no information on the equine larynx. This paper describes the expression and distribution of nerve fibres immunoreactive for vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), substance P (SP) and the adrenergic enzymatic marker dopamine beta-hydroxylase (DBetaH) in the mucosa of the equine larynx. The overall relative density of nerve fibres immunoreactive for the different antigens was VIP>>CGRP>SP>>DBetaH. There were differences in the distribution of nerve fibre types, although each antigen was found in nerve fibres adjacent to blood vessels and mucous glands. VIP -like immunoreactivity (VIP -Li) was particularly extensive in association with mucous glands. SP - and CGRP -like immunoreactivity (SP -Li, CGRP -Li) were also seen close to the epithelium, with occasional nerve fibres coursing beneath and between the epithelial cells. Fragments of SP -Li and CGRP -Li fibres were also present in large nerve fibre bundles and ganglionic cell clusters, but not in the neurons themselves. The density of nerve fibres immunoreactive for DBetaH was very low and restricted to blood vessels and mucous glands. There was marked variation in the density of nerve fibres at the different sites, with the greatest density, particularly for VIP, over the arytenoid cartilage. Immunoreactive nerve fibres were less plentiful over the epiglottis, and the density of all types of nerve fibres was low over the cricoid cartilage. Overall VIP -Li nerve fibres were the most plentiful.
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PMID:The distribution of nerve fibres immunoreactive for vasoactive intestinal peptide, calcitonin gene-related peptide, substance P and dopamine beta-hydroxylase in the normal equine larynx. 1060 5

Previous studies have revealed that some nerve fibres supplying the porcine oviduct may be of sensory origin. Therefore, the present study was aimed at disclosing the distribution of porcine 'oviductal' primary afferent neurons and the pattern(s) of putative coincidence of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and nitric oxide synthase (NOS) within these nerve cell bodies using combined retrograde tracing and double-labelling immunohistochemistry. We also investigated the existence and coexistence of immunoreactivities to tyrosine hydroxylase (TH) and dopamine beta-hydroxylase within the neurons because in some mammals, dorsal root ganglia (DRG) were previously found to contain perikarya immunoreactive (IR) to TH. Retrograde labelling revealed a population of large sensory neurons located in the Th(10)-L(3) DRG. There were no significant differences in the number or distribution between the ampulla- and isthmus-projecting neurons. Double-labelling immunoflourescence allowed several subpopulations of the studied perikarya to be distinguished. The largest one consisted of SP/CGRP-IR nerve cells, while the smallest subpopulation comprised NOS/VIP-IR neurons. Either SP/NOS, solely SP- or solely NOS-IR neurons were also found. Because identically coded nerve fibres have been observed within the wall of the porcine oviduct, based on their association with particular organ structures, it can be assumed that SP/CGRP-, SP/NOS- or solely NOS-IR neurons are involved in the antidromic relaxation of the oviductal vessels, SP-, NOS- or SP/CGRP-IR nerve cells control the oviductal tonus and that some neurons project beneath the epithelium and are involved in the transmission of sensory modalities from the oviduct to the spinal cord.
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PMID:Distribution of primary afferent neurons innervating the porcine oviduct and their immunohistochemical characterization. 1076 23

Little is known about neurogenic regulation of uterine contractility in mares. The present study investigated the distribution of adrenergic and peptidergic nerves in the mare uterus. Samples from the uterine horn, body and cervix were collected from 18 cyclic mares for immunohistochemistry. The uterus was well supplied with adrenergic nerves. A large number of tyrosine hydroxylase- and dopamine beta-hydroxylase-immunoreactive nerve bundles and fibres were present in the myometrium and endometrium in all regions of the uterus and cervix. These adrenergic nerve bundles and fibres travelled parallel to the muscle layers and were often associated with blood vessels. The density of peptidergic nerves was less than that of adrenergic nerves, but the pattern of distribution was similar. Neuropeptide Y-immunoreactive nerve fibres were the most abundant, whereas vasoactive intestinal polypeptide- and calcitonin gene-related peptide-immunoreactive nerve fibres were less frequently seen. Substance P-immunoreactive nerve fibres were the most sparse. Peptidergic nerves were distributed among the smooth muscle layers and near endometrial glands and were often associated with blood vessels in all regions of the uterus. The density of peptidergic nerve fibres was similar in the uterine horn and body but was slightly denser in the cervix. These findings indicate that uterine innervation may have an important role in controlling reproductive functions in mares.
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PMID:Immunohistochemical study of the distribution of adrenergic and peptidergic innervation in the equine uterus and the cervix. 1146 78

The present study was aimed at disclosing the distribution of paracervical neurons projecting to the ampulla and isthmus of the porcine oviduct and the pattern(s) of co-existence of tyrosine hydroxylase (TH), dopamine beta-hydroxylase (D beta H), neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP) and nitric oxide synthase (NOS) within these nerve cell bodies. The fluorescent retrograde tracer Fast Blue (FB) was injected into the wall of the ampullar (n = 3) and isthmal (n = 3) part of the organ in six sexually immature female pigs. After a survival period of three weeks paracervical ganglia (PCG) were collected. 10 microns-thick cryostat sections of the ganglia were examined for the presence of FB-positive (FB+) nerve cells under the fluorescent microscope. Tracered neurons were counted in every third section and processed for double-labelling immunofluorescence according to the method of Wessendorf and Elde. 78.6% of FB+ neurons were projecting to the isthmus while 21.4% of the studied population innervated the ampulla of the oviduct. Double-labelling immunofluorescence revealed the existence of the following different chemically coded subpopulations of the studied perikarya: TH+/D beta H+, TH+/NPY+, TH+/NOS+, TH+/NOS-, SP-/NOS+, SP+/CGRP+.
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PMID:Distribution and immunohistochemical characterisation of paracervical neurons innervating the oviduct in the pig. 1155 61

Noradrenaline (NA), a key neurotransmitter of the endogenous pain inhibitory system, acutely inhibits nociceptive transmission (including that mediated by substance P), potentiates opioid analgesia, and underlies part of the antinociceptive effects of the widely prescribed tricyclic antidepressants. Lesions of noradrenergic neurons, however, result in either normal or reduced pain behavior and variable changes in morphine antinociception, undermining the proposed association between noradrenaline (NA) deficiency and chronic pain (hyperalgesia). We used mice lacking the gene coding for dopamine beta-hydroxylase, the enzyme responsible for synthesis of NA from dopamine, to reexamine the consequences of a lack of NA on pain behavior. Here, we show that absence of NA in the central nervous system results in a substance P-mediated chronic hyperalgesia (decreased nociceptive threshold) to thermal, but not mechanical, stimuli and decreased efficacy of morphine. Contrary to studies that show substance P-mediated hyperalgesia requires intense stimuli, we found that even a mild stimulus is sufficient to evoke substance P-dependent hyperalgesia in the NA-deficient mice. Restoring central NA normalized both the nociceptive threshold and morphine efficacy, which is consistent with a tonic inhibitory effect of NA on nociceptive transmission. Unexpectedly, however, antagonists to the substance P receptor (the NK1 receptor) could achieve the same effect as NA replacement. We conclude that when unopposed by NA, substance P acting at the NK1 receptor causes chronic thermal hyperalgesia, and that the reduced opioid efficacy associated with a lack of NA is due to increased NK1-receptor stimulation.
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PMID:The NK1 receptor mediates both the hyperalgesia and the resistance to morphine in mice lacking noradrenaline. 1180 10


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