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)

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

The neurochemical properties of the ovine middle cervical ganglion (MCG) were studied using antibodies raised against tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DbetaH), neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and galanin (GAL). Double-labelling immunocytochemistry revealed that the vast majority (95.5 +/- 0.8%) of postganglionic sympathetic MCG neurons expressed simultaneously both catecholamine-synthesizing enzymes (neurons were TH/DbetaH-positive). A large population of noradrenergic neurons exhibited immunoreactivity (IR) to NPY (62.2 +/- 2.2%), but single NPY-positive perikarya-lacking noradrenergic markers were also observed (2.0 +/- 0.3%). None of the examined MCG neuronal somata contained SP, CGRP, GAL or VIP. A moderate number of noradrenergic nerve fibres located amongst neuronal cell bodies was also found. In small number of these terminals the presence of NPYor GAL (but not CGRP or VIP) was detected. The ovine MCG was numerously innervated with SP-immunoreactive nerve fibres which sometimes formed basket-like formations around postganglionic neurons. The MCG exhibited a sparse CGRP-immunoreactive innervation and lacked VIP-positive nerve terminals. In many aspects the chemical coding of MCG postganglionic neurons and nerve terminals resembles that found in other mammalian cervico-thoracic paravertebral ganglia, but some important species-dependent differences exist. The functional implications of these differences remain to be elucidated.
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PMID:Neurochemical properties of the middle cervical ganglion in the sheep. 1644 16

To determine whether noradrenaline (NA) is an essential neurotransmitter for addictive and appetitive behaviors, we measured drug and food seeking in transgenic mice lacking dopamine beta-hydroxylase (Dbh), the enzyme responsible for synthesizing NA. Using the conditioned place preference test (CPP), we show that Dbh -/- mice do not exhibit rewarding behavior to morphine, cocaine, or the mixed reuptake inhibitor bupropion. In spite of their lack of preference for drugs, Dbh -/- mice had an unaltered preference for food. Drug seeking was induced when NA was restored to the central nervous system of Dbh -/- mice by administration of l-threo-3,4-dihydroxyphenylserine (DOPS) and carbidopa. When a NK1 receptor antagonist was co-administered with morphine or cocaine, it produced aversive behavior in Dbh -/- mice while it abolished place preference in the controls. NK1 antagonists alone did not have any rewarding or aversive effect in the CPP suggesting that substance P opposes some of the unpleasant effects of morphine and cocaine. Our results show that NAergic transmission is necessary for motivated behaviors, the dysregulation of which is a co-morbid factor of many depressive states. The reversibility of this phenomenon, by restoring NA, indicates that even when this behavioral deficit is genetically determined it can be reversed.
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PMID:Noradrenaline is necessary for the hedonic properties of addictive drugs. 1689 13

The P450 eicosanoids epoxyeicosatrienoic acids (EETs) are endogenous lipid mediators produced in the brain by P450 epoxygenases and metabolized through multiple pathways, including soluble epoxide hydrolase (sEH). Epoxyeicosatrienoic acids play important functions in the brain, including regulation of cerebral blood flow and protection from ischaemic brain injury. We previously demonstrated that ischaemic preconditioning induces cytochrome P450 2C11 epoxygenase (CYP2C11) expression in the brain, and that pharmacological inhibition and genetic deletion of sEH increases EETs and protects against stroke-induced brain damage. However, the expression profiles of CYP2C11 and sEH in normal brain remain unknown. In agreement with previous reports in peripheral vessels, we here demonstrate by immunofluorescence double-labelling that within cerebral parenchymal microvessels, sEH-immunoreactivity (IR) is localized to the vascular smooth muscle layer. Unexpectedly, however, analysis of large cerebral conduit arteries such as the middle cerebral artery revealed CYP2C11 and sEH expression in extrinsic perivascular nerves. Double-labelling studies revealed that CYP2C11- and sEH-IR predominantly colocalized with neuronal nitric oxide synthase-IR within perivascular nerve fibres. Significant colocalization for CYP2C11 and sEH was also observed with the parasympathetic markers vasoactive intestinal peptide and choline actetyltransferase, in addition to the sensory fibre markers calcitonin gene-related peptide and substance P. No colocalization was observed for either CYP2C11 or sEH with the sympathetic nerve markers dopamine beta-hydroxylase or neuropeptide Y. The presence of enzymes involved in production and inactivation of EETs within extrinsic parasympathetic and sensory vasodilator fibres suggests a novel role for EETs in the neurogenic control of cerebral arteries.
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PMID:A novel role for P450 eicosanoids in the neurogenic control of cerebral blood flow in the rat. 1763 71

Palatine tonsils (PTs), together with ileal Peyer's patches, rank among the first colonization sites for infectious prions. After replicating in these lymphoid tissues, prions undertake the process of "neuroinvasion," which is likely mediated by the peripheral nerves connecting lymphoid tissues to the central nervous system (CNS). To study the connections between the tonsils and the CNS, we injected fluorescent tracers into the PTs of lambs; the highest number of Fast Blue (FB)-labeled neurons was found in cranial cervical ganglia (CCG), whereas a progressively decreasing number of cells were detected in proximal glossopharyngeal, proximal vagal, trigeminal, pterygopalatine, and cervicothoracic ganglia. Immunohistochemistry was carried out on tonsil and ganglia cryosections. Immunoreactivity (IR) for tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), neuronal nitric oxide synthase (nNOS), calcitonin gene-related peptide (CGRP), substance P (SP), and calcium-binding protein S100 (S100), was observed in the fibers around and within PT lymphoid nodules. In the trigeminal, proximal glossopharyngeal and vagal ganglia the retrogradely-labeled neurons showed nNOS-, SP- and CGRP-IR. In all ganglia some retrogradely-labeled neurons showed nNOS-, SP- and CGRP-IR co-localization. It is worth noting that only 66+/-19% and 75+/-13% of retrogradely-labeled neurons in CCG showed TH- and DBH-IR, respectively. The present results allow us to attribute PT innervation mainly to the sympathetic component and to the glossopharyngeal, vagal and trigeminal cranial nerves. Furthermore, these data also provide a plausible anatomic route through which infectious agents, such as prions, may access the CNS, i.e. by traveling along several cranial and sympathetic nerves, as well as by migration via glial cells.
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PMID:Characterization of sheep (Ovis aries) palatine tonsil innervation. 1936 24

In this study, the presence of several neurotransmitters and transmitter synthesizing enzymes was studied in hypoglossal nucleus (HN) of the juvenile (4 months old) female pigs (n = 3). Double-labeling immunofluorescence revealed neurones expressing cholinacetyltranspherase (ChAT), calcitonin gene-related peptide (CGRP), nitric oxide synthase (NOS), and somatostatin (SOM). Nerve fibers within HN were ChAT, CGRP, NOS, SOM, substance P (SP), Leu-5-enkephalin (Leu-5-Enk), ss-dopamine hydroxylase (DssH), neuropeptide Y (NPY) positive. Virtually all the perikarya contained ChAT, whereas CGRP was present in 47% of the neurones. Nerve cell bodies containing NOS or SOM were only occasionally observed. Immunoreactive nerve fibers were found in a close vicinity of the perikarya, often forming baskets around nerve cell bodies. The results obtained were compared with similar data obtained in other species. The presence of immunoreactive structures, origin of the nerve fibers, and functional significance of the findings are discussed.
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PMID:Immunohistochemical characterization of neurones in the hypoglossal nucleus of the pig. 2007 Feb 90

Sympathetic chain ganglia (SChG) neurons projecting to the descending colon of the pig were studied by means of retrograde tracing (Fast Blue, FB) and double-labelling immunofluorescence methods. FB was injected into the gut wall and after three weeks survival time the animals were transcardially perfused with paraformaldehyde and the bilateral sympathetic trunks were collected. The FB-positive neurons were localised only in the lumbar (L(1)-L(5)) ganglia of the sympathetic trunk and appeared either as small (30-50 microm in diameter) round-shaped perikarya forming clusters localised in caudal-ventral area or, rarely, as bigger (50-80 microm) and dispersed solitary irregular perikarya. Immunohistochemical staining revealed the catecholaminergic (tyrosine hydroxylase-/dopamine beta-hydroxylase-immunoreactive) character of the great majority of FB-positive neurons which preferentially co-expressed neuropeptide Y. In addition, none of the FB-positive perikarya was immunopositive to galanin, somatostatin, choline acetyltransferase, vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, leu(5)-enkephalin, nitric oxide synthase, substance P and calcitonin-generelated peptide.
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PMID:Distribution pattern and chemical coding of neurons of the sympathetic chain ganglia supplying the descending colon in the pig. 2046 Feb 18

The distribution and chemical phenotypes of sympathetic and dorsal root ganglion (DRG) neurons innervating the equine ileocecal junction (ICJ) were studied by combining retrograde tracing and immunohistochemistry. Immunoreactivity (IR) for tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), neuronal nitric oxide synthase (nNOS), calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY) was investigated. Sympathetic neurons projecting to the ICJ were distributed within the celiac (CG), cranial mesenteric (CranMG), and caudal mesenteric (CaudMG) ganglia, as well as in the last ganglia of the thoracic sympathetic chain and in the splanchnic ganglia. In the CG and CranMG 91 +/- 8% and 93 +/- 12% of the neurons innervating the ICJ expressed TH- and DBH-IR, respectively. In the CaudMG 90 +/- 15% and 94 +/- 5% of ICJ innervating neurons were TH- and DBH-IR, respectively. Sympathetic (TH-IR) fibers innervated the myenteric and submucosal ganglia, ileal blood vessels, and the muscle layers. They were more concentrated at the ICJ level and were also seen encircling myenteric plexus (MP) and submucosal plexus (SMP) descending neurons that were retrogradely labeled from the ICJ. Among the few retrogradely labeled DRG neurons, nNOS-, CGRP-, and SP-IR nerve cells were observed. Dense networks of CGRP-, nNOS-, and SP-IR varicosities were seen around retrogradely labeled prevertebral ganglia neurons. The CGRP-IR fibers are probably the endings of neurons projecting from the intestine to the prevertebral ganglia. These findings indicate that this crucial region of the intestinal tract is strongly influenced by the sympathetic system and that sensory information of visceral origin influences the sympathetic control of the ICJ.
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PMID:Sympathetic innervation of the ileocecal junction in horses. 2073 99


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