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)

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

Axonally transported toxins can be used to make selective lesions of the nervous system. Collectively, these techniques are termed 'molecular neurosurgery' because they exploit the surface molecular identity of neurons to selectively destroy specific types of neurons. Suicide transport, is anatomically selective but not type-selective. The most widely used suicide transport agents are the toxic lectins (ricin, volkensin) and the immunotoxin, OX7-saporin. The toxic lectins and saporin are ribosome inactivating proteins that irreversibly inhibit protein synthesis. The toxic lectins have binding subunits but saporin requires a targeting vector to gain entrance into cells. Immunolesioning uses monoclonal anti-neuronal antibodies to deliver saporin selectively into neurons that express a particular target surface antigen. Neuropeptide-saporin conjugates selectively destroy neurons expressing the appropriate peptide receptors. Notable experimental uses of these agents include analysis of the function of the cholinergic basal forebrain (192-saporin) and pain research (anti-DBH-saporin, substance P-saporin). It is likely that more immunolesioning and neuropeptide-toxin conjugates will be developed in the near future.
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PMID:Neuronal lesioning with axonally transported toxins. 1107 97

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

Here we examine whether a permanent reduction in the noradrenergic (NA) innervation of the spinal cord leads to a chronic decreased nociceptive threshold. NA denervation of rats was achieved by intrathecal injection of dopamine beta-hydroxylase antibodies conjugated to the toxin saporin. A subset of animals also underwent unilateral L5 spinal nerve ligature to induce sustained neuropathic pain behavior. NA fibers and terminals were lost throughout the spinal cord 2 weeks after toxin application and were still absent 12 months later, indicating that regeneration did not occur. There was also a widespread loss of NA terminals in the cerebral cortex, whereas innervation of the hypothalamus and amygdala were close to normal and NA innervation of the brainstem was moderately reduced. There was extensive loss of NA cells in the locus coeruleus and A5 and A7 cell groups. Dopaminergic and serotoninergic innervation was normal. Intracerebroventricular injection of the toxin resulted in additional NA reduction in the hypothalamus, amygdala, and A1 and A2 cell groups. Long-term removal of NA afferents did not affect nociceptive thresholds. Neuropathic animals showed greater mechanical hyperalgesia in the affected hindpaw only during the first 60 days after toxin. Rats lacking NA spinal afferents were less responsive to the antinociceptive effects of morphine, especially in the neuropathic hindpaw, and did not display opioid-dependent stress analgesia. Finally, in the spinal cord of toxin-treated rats, immunoreactivity for substance P was decreased, whereas that of its receptor (NK1) was increased. These animals exhibited antinociception to a low dose of an NK1 receptor antagonist. Our results suggest that NA contributes only modestly to determining the nociceptive threshold and that its antinociceptive effects are closely linked to opioidergic and tachykinergic neurotransmission.
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PMID:Long-term effects of decreased noradrenergic central nervous system innervation on pain behavior and opioid antinociception. 1268 95

This study presents the distribution and chemical coding of neurons in the porcine intramural ganglia of the urinary bladder trigone (IG-UBT) demonstrated using combined retrograde tracing and double-labelling immunohistochemistry. Retrograde fluorescent tracer Fast Blue (FB) was injected into the wall of both the left and right side of the bladder trigone during laparotomy performed under pentobarbital anaesthesia. Ten-microm-thick cryostat sections were processed for double-labelling immunofluorescence with antibodies against tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), neuropeptide Y (NPY), somatostatin (SOM), galanin (GAL), vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), calcitonin gene-related peptide (CGRP), substance P (SP), Leu5-enkephalin (LENK) and choline acetyltransferase (ChAT). IG-UBT neurons formed characteristic clusters (from a few to tens neuronal cells) found under visceral peritoneum or in the outer muscular layer. Immunohistochemistry revealed four main populations of IG-UBT neurons: SOM- (ca. 35%), SP- (ca. 32%), ChAT- and NPY- immunoreactive (-IR) (ca. 23%) as well as non-adrenergic non-cholinergic nerve cells (ca. 6%). This study has demonstrated a relatively large population of differently coded IG-UBT neurons, which constitute an important element of the complex neuro-endocrine system involved in the regulation of the porcine urogenital organ function.
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PMID:Distribution and chemical coding of neurons in intramural ganglia of the porcine urinary bladder trigone. 1504 94

The present study was aimed at disclosing the chemical coding of nerve structures in the porcine ciliary ganglion (CG) using immunohistochemical methods. The substances under investigation included markers of "classical" neurotransmitters, choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DbetaH) as well as neuropeptides, somatostatin (SOM), galanin (GAL), substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY). Immunoreactivity to ChAT and VAChT was found virtually in all the neuronal somata and in numerous intraganglionic, varicose nerve fibres which often formed basket-like formations around the nerve cell bodies. Many CG neurons contained immunoreactivity for SOM (46%) or GAL (29%). Interestingly, a small number (approx. 1%) of the cholinergic somata stained for TH but not for DbetaH; nevertheless, some extra- and intraganglionic nerve fibres displayed immunoreactivity for DbetaH or TH. The CG perikarya stained neither for vasoactive intestinal polypeptide (VIP) nor for neuropeptide Y (NPY), but some NPY- or VIP-positive nerve terminals were observed within nerve bundles distributed outside the ganglion. SP- and CGRP-immunoreactivity was found in some intraganglionic nerve fibres only. The present study revealed that the porcine CG consists of cholinergic neurons many of which contain SOM and GAL. Thus, it can be assumed that in the pig, these neuropeptides are involved, complementary to acetylocholine, in the parasympathetic postganglionic nerve pathway to structures of the eye including the ciliary and iris sphincter muscles.
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PMID:Immunohistochemical characterization of neurons in the porcine ciliary ganglion. 1579 76


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