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)

The effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle or of a sham lesion on the neuropeptide content of the striatum and substantia nigra was investigated with or without 6 months L-3,4-dihydroxyphenylalanine (L-DOPA; 200 mg/kg per day) plus carbidopa (25 mg/kg per day) treatment. [Met5]- and [Leu5]enkephalin, substance P (SP), neurotensin (NT) and cholecystokinin (CCK) were measured by a combined HPLC/RIA method. Neurotensin levels were increased in the striatum, and [Leu5]enkephalin, and SP levels were reduced in the substantia nigra as a consequence of the lesion, while the levels of other peptides were unaltered. Administration of L-DOPA to sham-operated rats bilaterally increased SP levels in striatum and substantia nigra, and [Met5]enkephalin and CCK content in substantia nigra. L-DOPA treatment of 6-OHDA-lesioned rats increased [Met5]- and [Leu5]enkephalin and CCK levels in the striatum ipsilateral to the lesion but not on the intact side. In the substantia nigra, the lesion-induced decrease in [Leu5]enkephalin and SP was reversed by L-DOPA treatment, [Met5]enkephalin and CCK levels ipsilateral to the lesion were further enhanced, and there was an increase in NT ipsilateral to the lesion. Cryptic [Met5]- and [Leu5]enkephalin increased in the ipsilateral striatum following an 6-OHDA lesion. L-DOPA treatment did not alter cryptic enkephalin levels or the lesion-induced increase in cryptic [Met5]enkephalin, while cryptic [Leu5]enkephalin was further increased in lesioned animals given L-DOPA. These results suggest that the pattern of change in basal ganglia peptides in Parkinson's disease is not due solely to the destruction of the nigrostriatal pathway, the drug treatment of the disease or a combination of these factors.
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PMID:Effects of a unilateral 6-hydroxydopamine lesion and prolonged L-3,4-dihydroxyphenylalanine treatment on peptidergic systems in rat basal ganglia. 138 71

To investigate synaptic mechanisms in taste buds and collect information about synaptic transmission in these sensory organs, we have examined taste buds of the mudpuppy, Necturus maculosus for the presence of neurotransmitters and neuromodulators. Immunocytochemical staining at the light microscopic level revealed the presence of serotonin-like and cholecystokinin-like (CCK) immunoreactivity in basal cells in the taste bud. Nerve fibers innervating taste buds were immunoreactive for vasoactive intestinal peptide-like (VIP), substance P-like, and calcitonin gene-related peptide-like (CGRP) or compounds closely related to these substances. Immunoreactivity for tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) in the taste cells and nerve fibers was absent. These data suggest that serotonin, CCK, VIP, substance P, and CGRP are involved in synaptic transmission or neuromodulation in the peripheral organs of taste. No evidence was found for cholinergic or adrenergic mechanisms on the basis of the absence of immunocytochemical staining for key enzymes involved in these two transmitter systems.
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PMID:Immunocytochemical survey of putative neurotransmitters in taste buds from Necturus maculosus. 138 95

To investigate the role of neuropeptides in allergic inflammation, we examined the effect of peptides on eosinophil chemotaxis. Eosinophils were purified from the blood of allergic and normal subjects using a discontinuous Percoll density gradients. Chemotaxis was induced by platelet-activating factor (PAF) and leukotriene B4, and was assayed by a modified Boyden's chamber technique. Four neuropeptides were examined in this study: substance P (SP), neurokinin A, calcitonin gene-related peptide (CGRP), and cholecystokinin octapeptide. Peptides alone (10 nM to 10 microM) were not chemotactic for eosinophils. However, when eosinophils were pre-treated with peptides (100 nM) at 37 degrees C for 30 min, chemotactic response to PAF (10 nM) was significantly enhanced (p < 0.01) in allergic subjects; % control by SP, neurokinin A, CGRP and cholecystokinin octapeptide was 269 +/- 42, 243 +/- 32, 227 +/- 21, and 251 +/- 42, respectively (n = 8). Similar results were obtained in leukotriene B4-induced eosinophil chemotaxis. In contrast, no enhancement was observed in normal subjects. Potentiating effect of SP and CGRP on PAF-induced eosinophil chemotaxis in allergic subjects was significantly attenuated by SP antagonist [D-Pro2,D-Trp7,9]-SP and human CGRP (8-37) receptor antagonist, respectively. Neutral endopeptidase inhibitors (phosphoramidon, leupeptin, and bestatin) failed to significantly augment the PAF-induced eosinophil chemotaxis when the cells were pretreated with various peptides and neutral endopeptidase inhibitors. The C-terminal fragment of SP (SP6-11) had an effect similar to that of the intact SP molecule, whereas no potentiating effect by the N-terminal of SP (SP1-9) was observed. These results suggest that neuropeptides may play a significant role in eosinophil infiltration by priming cells in allergic inflammation.
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PMID:Neuropeptides modulate human eosinophil chemotaxis. 138 21

To further address the hypothesis that cholecystokinin (CCK) in the medullary dorsal horn (MDH) arises from intrinsic or higher-order neurons, CCK-8-specific radioimmunoassay (RIA) and immunohistochemical (IHC) experiments were carried out in adult rats after trigeminal tractotomy. RIA of punches from deafferented superficial layers of the MDH revealed no significant change in CCK levels vs. the control right side. In this same area, IHC revealed modest reductions in CCK, gastrin, and substance P staining. Calcitonin gene-related peptide (CGRP) staining was reduced substantially. Gastrin immunoreactive cell bodies, present normally in inner lamina II, were reduced in number. RIA and IHC methods were also used to assess MDH CCK concentrations in adult rats subjected to left infraorbital nerve section at birth. The left medulla contained significantly higher levels of CCK than the control right medulla (1.27 +/- 0.19 vs. 0.97 +/- 0.11 ng/mg protein). IHC revealed a dense band of CCK-like staining in laminae I and II ipsi- and contralateral to the lesion. Thus, neonatal deafferentation elevates medullary CCK. To determine if the neonatal lesion-induced increase in medullary CCK is due to primary afferent or higher-order reorganization, RIA and IHC experiments were run after infraorbital nerve section at birth and trigeminal tractotomy in adulthood. RIA revealed no significant change in CCK levels caudal to the tractotomy, although they were higher than control levels in 9 of 12 cases. IHC revealed modest reductions in CCK, substance P, and gastrin staining that resembled the reductions observed in tractotomy-alone cases. These data suggest that 1) most MDH CCK is of non-primary afferent origin, 2) gastrin immunoreactivity in layer II probably originates in CCK-containing cells intrinsic to layer II, the expression of which is dependent upon trigeminal primary afferent input, 3) neonatal V deafferentation induces increased CCK in the superficial MDH, reflecting reorganized intrinsic or higher-order inputs, and 4) higher-order substance P in the MDH is robust.
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PMID:Cholecystokinin concentrations and peptide immunoreactivity in the intact and deafferented medullary dorsal horn of the rat. 147 68

The present study determines the effects of sciatic nerve stimulation at intensities that activate A-fibers alone or both A- and C-fibers on immunostaining for substance P (SP), cholecystokinin-octapeptide (CCK-8), galanin (GAL), dynorphin (DYN) and vasoactive intestinal polypeptide (VIP) in the superficial dorsal horn of the rat spinal cord. The goal of this study is to provide a more precise spatial localization of the sites of release or accumulation of these compounds in relation to specific types of stimuli. Following A-fiber stimulation, there was no significant change in immunostaining for any of these compounds. However, A- and C-fiber stimulation resulted in major changes. For SP, CCK-8, GAL and DYN there was a large and significant loss of immunostaining in medial regions of the dorsal horn. This is the area where sciatic nerve primary afferent fibers terminate and the depletion is probably correlated with activity in these fibers. By contrast, VIP immunostaining is increased in the lateral part of the superficial cord, which is outside of the central sciatic afferent fiber terminations. This indicates that the increase is not in the fine sciatic sensory axons that are directly stimulated. As a final point, the fact that C-fiber but not A-fiber stimulation causes marked changes in the immunocytochemical distribution of all these compounds is further evidence, albeit indirect, that they are involved in nociceptive information processing.
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PMID:The effects of A- and C-fiber stimulation on patterns of neuropeptide immunostaining in the rat superficial dorsal horn. 150 92

Enteroendocrine cells represent the most heterogeneous population of terminally differentiated cells in the mouse intestinal epithelium. Each of the approximately 15 different enteroendocrine cell subpopulations shows characteristic distributions along both the cephalocaudal and crypt-to-villus (in the small intestine) or crypt-to-surface epithelial cuff (in the colon) axes of the gut. These cells provide a sensitive model for studying how the continuously renewing gut epithelium is able to establish and maintain its spatial differentiation. Enteroendocrine cells are derived from the same multipotent stem cell that gives rise to enterocytes and goblet and Paneth cells. Regional differences in enteroendocrine cell number and type reflect positional differences in the differentiation programs of this lineage. To better understand the nature of these programs, we used multilabel immunocytochemical methods to examine the accumulation of endogenous neuroendocrine products as well as the product of a liver fatty acid binding protein/human growth hormone transgene in enteroendocrine cells located in proximal colonic glands. The results suggest that serotonin, substance P-, glucagon-like peptide-1 (GLP-1)-, peptide tyrosine tyrosine (PYY)-, neurotensin-, and cholecystokinin (CCK)-producing cells can all arise from a single stem cell located within a given gland. Based on pairwise comparison of the coexpression of each of these six products in individual cells as well as their ability to support transgene expression, it appears that the enteroendocrine lineage has two branches; one branch produces substance P and serotonin cells while the other yields GLP-1, PYY, neurotensin, and CCK cells.
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PMID:Immunocytochemical studies suggest two pathways for enteroendocrine cell differentiation in the colon. 151 28

The Wobbler mouse possesses an inherited form of motoneuron disease that expresses itself most dramatically in the forelimbs. Previous immunocytochemical (ICC) studies have shown that neuronal processes containing substance P (SP), thyrotropin releasing hormone (TRH) and serotonin (5-HT) seem to sprout in the ventral horn of the cervical spinal cord taken from the Wobbler mouse. By radioimmunoassay, increased concentrations of spinal SP, TRH, and 5-HT, as well as leucine and methionine enkephalins (LE, ME) have been documented. The present ICC study quantifies the numbers of neuronal processes in the Wobbler cervical spinal cord and brainstem which contain SP, 5-HT, LE, ME and other neuropeptides (cholecystokinin, CCK; neuropeptide Y; galanin; calcitonin gene-related peptide, CGRP). It is proposed that those processes that sprout early in the mononeuron disease (5-HT, LE, ME, CCK and also TRH according to other studies) may be involved in the etiology. In addition, it is hypothesized that the loss of CGRP within the ventral horn may represent the loss of a trophic factor that is important to the survival motoneurons and may influence the increase of fiber densities around the dying motoneurons.
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PMID:Decreased immunoreactive (IR) calcitonin gene-related peptide correlates with sprouting of IR-peptidergic and serotonergic neuronal processes in spinal cord and brain nuclei from the Wobbler mouse during motoneuron disease. 152 46

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a new member of the secretin/glucagon peptides family, being most homologous to vasoactive intestinal peptide (VIP). The present study was designed to investigate a possible effect of PACAP on the rat gastrointestinal smooth muscle in vitro. We demonstrated that 1) PACAP reduced basal smooth-muscle contractions in all portions of the gastrointestinal tract, but the effect of VIP was region-specific. The inhibitory effect of PACAP in midcolon was approximately 100 times greater than that of VIP. 2) PACAP significantly inhibited smooth-muscle contractions induced by acetylcholine or carbachol. The inhibitory effect of PACAP was not affected by hexamethonium and was additive to the inhibitory effect of atropine and pirenzepine. 3) PACAP inhibited smooth-muscle contractions induced by substance P, cholecystokinin, and galanin, even after atropine treatment. Although the exact mechanism of the inhibitory action of PACAP remains to be clarified, PACAP appears to exert its effect in the rat at a site other than muscarinic receptors, probably through a direct effect on gastrointestinal smooth muscle in vitro.
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PMID:Pituitary adenylate cyclase-activating polypeptide relaxes rat gastrointestinal smooth muscle. 152 72

The topographical distribution of neuropeptide-containing cell bodies, fibers and terminals was studied in human parabrachial nuclei and the pontine tegmentum with immunohistochemical stainings. Brains of seven adult human subjects of 35-72 years were fixed within 2 h post mortem. Serial sections were immunostained by antisera of 14 different neuropeptides--oxytocin, vasopressin, thyrotropin-releasing hormone, angiotensin II, calcitonin gene-related peptide, beta-endorphin, dynorphin A, dynorphin B, leucine-enkephalin, alpha-melanocyte stimulating hormone, substance P, neuropeptide Y, cholecystokinin and galanin--alternately. All of these peptides were found to be present in nerve fibers and terminals, but only two, angiotensin II and dynorphin B, in cell bodies of the parabrachial nuclei. Calcitonin gene-related peptide-, neuropeptide Y-, cholecystokinin- and galanin-immunoreactive cells were present in other areas of the pontine tegmentum, like the motor trigeminal nucleus, locus coeruleus, periventricular gray matter but not in the parabrachial nuclei. Peptidergic fibers were distributed unevenly throughout the pontine tegmentum having unique, individual distribution patterns. In the parabrachial nuclei, substance P, neuropeptide Y, cholecystokinin and galanin showed the highest density of immunoreactive neuronal networks. Moderate to low concentrations of immunoreactive processes were detected by calcitonin gene-related peptide, alpha-melanocyte stimulating hormone, dynorphin B, thyrotropin releasing hormone, leucine-enkephalin, dynorphin A, angiotensin II, beta-endorphin, vasopressin and oxytocin antisera, respectively. Other pontine tegmental areas, like the locus coeruleus, dorsal tegmental, pontine raphe and motor trigeminal nuclei as well as the central gray of the tegmental region exhibited a varying assortment of neuropeptides with distinct, individual localization patterns. Their detailed topographical distributions are mapped and given in coronal sections.
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PMID:Immunohistochemical study on the distribution of neuropeptides within the pontine tegmentum--particularly the parabrachial nuclei and the locus coeruleus of the human brain. 154 21

Myenteric plexus neurons derived from neonatal guinea pigs, when exposed to serum, demonstrated a characteristic pattern of growth, including a proliferating outgrowth zone of glial cells, peripheral extension of dendritic processes, and progressive dendritic growth. Serum effects upon dendritic growth, measured morphometrically, was strongly dose- and temporally dependent. Dendritic density was increased 10-fold (120 hr) by the addition of 6% serum, while mean dendritic length was increased 3-fold. Development of cholinergic function was reflected by release of [3H]ACh in response to cholecystokinin octapeptide, vasoactive intestinal peptide, substance P, and calcitonin gene-related peptide (10(-10) and 10(-8) M).
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PMID:Dendritic outgrowth of myenteric plexus neurons in primary culture. 159 70


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