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)

Light and electron microscopic peroxidase-antiperoxidase immunocytochemistry has been used to localize choline acetyltransferase, substance P and enkephalin in the hypoglossal nucleus of the rat. Choline acetyltransferase immunoreactivity was observed in motoneurone cell bodies and proximal dendrites, in large varicosities in the surrounding neuropil and in nerve terminals in synaptic contact with immunostained motoneurones. Most choline acetyltransferase immunostained terminals which made synaptic contact with motoneurone cell bodies and proximal dendrites possessed prominent subsynaptic cisterns and belong to the terminal type referred to in the literature as C or L. Substance P and enkephalin immunoreactivity did not occur in motoneurones but was seen in fibres and synaptic terminals. Substance P immunoreactive fibres made multiple axosomatic contacts while enkephalin immunoreactive terminals made synaptic contact mainly with large and small dendrites. C terminals were not stained for either substance P or enkephalin. This study provides immunocytochemical support for the classic identification of hypoglossal motoneurones as cholinergic and in addition shows that these neurones are innervated by a number of morphologically and chemically distinct terminal types. C terminals have previously been shown to contain cholinesterase and our demonstration that these terminals contain choline acetyltransferase thus provides additional evidence for their cholinergic nature and for a cholinergic innervation of hypoglossal motoneurones. The origin of the immunoreactive terminals was not identified in this study but possible candidates include the raphe nuclei for substance P. and propriobulbar interneurones for choline acetyltransferase.
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PMID:Inputs to motoneurones in the hypoglossal nucleus of the rat: light and electron microscopic immunocytochemistry for choline acetyltransferase, substance P and enkephalins using monoclonal antibodies. 242 Nov 99

The choice of which transmitter will be expressed by a neuron is influenced by diffusible differentiating factors produced by a variety of nonneuronal cells. In this study we show that human, bovine, and rat brains contain a soluble heparin-binding factor that stimulates cholinergic and peptidergic expression. We also show that neuronal contact with other cell membranes influences neurotransmitter development and acts synergistically with the effects of the soluble brain factor. Exposure of cultured sympathetic neurons to purified plasma membranes derived either from cultured Schwann cells or from cultured sympathetic neurons promoted expression of choline acetyltransferase (CAT), a cholinergic trait, and of substance P (SP). CAT activity and SP were also stimulated by a 50-kDa soluble protein that was purified 14,000-fold from human, calf, and rat brain by heparin-Sepharose affinity chromatography. CAT activity after concurrent treatment with plasma membranes and the soluble factor far exceeded the sum of the enzyme activities after the individual treatments, suggesting that membrane molecules and the factor facilitated each other. Thus, cell-surface molecules, which have been shown previously to influence neuronal morphogenesis and neurite elongation, may also help determine the transmitter phenotype of the neuron. Moreover, cell-surface molecules may modulate the effects of diffusible differentiating factors.
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PMID:Isolated plasma membranes regulate neurotransmitter expression and facilitate effects of a soluble brain cholinergic factor. 242 54

Whether or not adrenal medullary (chromaffin) cells which respond to nerve growth factor (NGF) both in vitro and in vivo require NGF for their normal development is controversial. Systemic deprivation of endogenous NGF by injection of anti-NGF antibodies into rat fetuses or by transfer of anti-NGF to the offspring of autoimmunized mothers has provided conflicting results. We have reinvestigated the effects of a specific antiserum to NGF on the morphology, catecholamine (CA) and neuropeptide (Met-enkephalin, Met-ENK; substance P, SP) content, and choline acetyltransferase (ChAT) activity of the rat adrenal medulla. Fetuses were injected with anti-NGF antibodies on day 17 of gestation and postnatally at daily intervals for 7 days. The histological appearance of adrenal medullae of anti-NGF injected animals was not altered as compared to controls. Ultrastructurally, no degenerative changes or developmental retardation of chromaffin cells could be detected. However, numbers of chromaffin granules per micron 2 of cytoplasmic area were greater and the mean diameters of the cores of adrenaline storage granules were smaller in antibody-treated than in control animals. CA and SP content, ratios of adrenaline to noradrenaline and ChAT activities were identical in anti-NGF-treated and control animals. Anti-NGF antibodies caused a reduction of adrenal Met-ENK by 40% as compared to controls. Superior cervical ganglia from the same animals were used to document immunosympathectomy induced by the antiserum. They displayed the well-established structural alterations and a marked reduction of the CA content. We conclude that administration of anti-NGF antibodies to embryonic and early postnatal rats induces only subtle changes in the ultramorphology of chromaffin cells without altering the development of normal CA levels. The small, yet significant effects of anti-NGF antibodies on adrenal Met-ENK, however, may suggest a role for endogenous NGF in the regulation of opioid peptide metabolism in developing chromaffin cells.
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PMID:Effects of pre- and postnatal administration of antibodies to nerve growth factor on the morphological and biochemical development of the rat adrenal medulla: a reinvestigation. 242 96

We have developed procedures for dissociating neurons from the myenteric plexus of the small intestine of newborn rats and for growing those neurons in cell cultures for up to 3 months. Neurons in these cultures retain many of the differentiated properties of myenteric neurons in vivo. This is the first of a series of 3 papers describing those properties. In this paper, we describe the morphology of cultured neurons that we have observed with light and electron microscopy; we also describe the patterns of straining observed when immunocytochemical techniques were used to localize neurotransmitter candidates in the cultured neurons. Intracellular injections of a fluorescent dye, Lucifer yellow, revealed that many of the cultured neurons had morphologies similar to those of myenteric neurons in vivo. When thin sections of cultures were viewed in an electron microscope, many neurons were observed to have numerous small (40-60 nm), clear synaptic vesicles and/or large (80-150 nm), opaque-cored (p-type) vesicles. Synaptic profiles were most often observed on neuronal somata. Neurons containing immunoreactive serotonin, substance P, somatostatin, enkephalin, bombesin and gastrin/cholecystokinin were observed in about the same proportions as they occur in the intact myenteric plexus. Neurons containing immunoreactive vasoactive intestinal polypeptide were found in higher numbers than reported in vivo. Neurons containing immunoreactive neurotensin, secretin and glutamate decarboxylase were not observed. An antiserum directed against choline acetyltransferase stained 40-50% of the neurons. We conclude that myenteric neurons continue to express much of their normal differentiated properties even when they are removed from the gut, dissociated into a suspension of single cells and grown in culture. Such cultures will be useful for correlating the morphological, biophysical, pharmacological and synaptic properties of individual myenteric neurons and for testing the ability of altered environmental conditions to change those properties.
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PMID:Neurons dissociated from rat myenteric plexus retain differentiated properties when grown in cell culture. I. Morphological properties and immunocytochemical localization of transmitter candidates. 242 14

Atriopeptin, the atrial natriuretic peptide, is a circulating hormone that plays an important role in the regulation of fluid and electrolyte balance. Immunohistochemical studies have shown that large, multipolar atriopeptin-like immunoreactive (APir) neurons are present in areas of the midbrain corresponding to the large neurons of the pedunculopontine tegmental (PPT) and lateral dorsal tegmental (TLD) nuclei, all of which can be stained immunohistochemically for choline acetyltransferase-like immunoreactivity (ChATir). A subpopulation of these cholinergic PPT and TLD neurons are also known to contain substance P-like immunoreactivity (SPir). Using an immunofluorescent technique that allows simultaneous localization of two antigens, we have studied the relationship between APir, SPir and ChATir in the pontine tegmentum of the rat. We have found that the large multipolar APir neurons of the pontine tegmentum are identical to the ChATir neurons of the PT and TLD nuclei and a subpopulation of the APir neurons in PPT and TLD neurons are also SPir.
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PMID:Colocalization of atriopeptin-like immunoreactivity with choline acetyltransferase- and substance P-like immunoreactivity in the pedunculopontine and laterodorsal tegmental nuclei in the rat. 242 24

Very few double-antigen staining methods are available that are applicable to both light and electron microscopy. The objective of this study was to develop for localization of two neural antigens simultaneously a procedure which would be sensitive, simple to perform, offer permanent reaction products, and permit correlated light and ultrastructural analysis. The method employs sequential immunoperoxidase staining without antibody elution, in which the first sequence of antibodies is visualized with 3,3'-diaminobenzidine (DAB) and the second with benzidine dihydrochloride (BDHC). The DAB reaction product (brown and diffuse) was easily distinguishable from the BDHC deposit (blue, granular, and more electron-dense) by both light and electron microscopy. The procedure was used to simultaneously localize choline acetyltransferase-and either substance P or tyrosine hydroxylase in rat brain at both light and ultrastructural levels. Control experiments demonstrated the absence of both color mixing and antibody crossreactions, even when both primary antibodies were from the same species. This study demonstrates the usefulness of BDHC as a chromogen for immunoperoxidase staining either alone or in combination with DAB, and describes a double method which should have wide applicability for detailed studies of most pairs of antigens at both light and ultrastructural levels.
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PMID:A light and electron microscopic procedure for sequential double antigen localization using diaminobenzidine and benzidine dihydrochloride. 243 10

High cell density, with attendant aggregation, selectively increases expression of substance P (SP) and choline acetyltransferase (ChAT) in virtually pure neonatal sympathetic neuronal cultures. To investigate the specific role of cell contact in selective transmitter expression, SP content and ChAT activity were examined in such cultures under various conditions. At high neuronal density SP content, detectable 6 h after plating, doubled during the first two culture days and subsequently increased more than 10-fold. Similarly, ChAT activity appeared de novo after two days and rose rapidly thereafter. The increases closely paralleled perikaryal aggregation, suggesting that cell contact might be the critical factor. Moreover, interference with aggregation physically, using methylcellulose, or chemically, using tunicamycin, inhibited the increases in SP content and ChAT activity without affecting neuronal survival. Thus, cell contact appears to mediate the expression of ChAT and the rise of SP in high-density neuronal cultures. To determine whether interaction of membrane component(s) elicited the rises in ChAT activity and SP content, membranes extracted from the neonatal superior cervical ganglion (SCG) were added to cultures of varying densities. After 3 days in high-density cultures, membranes doubled the increases in ChAT and SP. Moreover, even in lower-density cultures, membranes elicited the appearance of ChAT activity. Specificity was defined by examining membranes extracted from a variety of neonatal rat tissues. Dorsal root ganglia membranes were most effective in stimulating ChAT, followed by membranes from the SCG, kidney and brain. Membranes derived from the adrenal gland, liver and spinal cord had no effect. Our findings suggest that interaction of cell membrane components regulates phenotypic expression in aggregating neurons.
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PMID:Membrane contact regulates transmitter phenotypic expression. 243 Jun 80

Antibodies against substance P and choline acetyltransferase (ChAT) have been used in a sequential double-immunocytochemical ultrastructural study of the rat forebrain. The peroxidase-anti-peroxidase procedure was used for both antigens, however, two different substrates for the peroxidase reactions were used. The substance P-immunoreactive sites were first localized using 3,3'-diaminobenzidine as the substrate, then the ChAT-immunoreactive sites were localized using benzidine dihydrochloride. The reaction product formed by the two substrates was distinguishable in both the light and electron microscopes. Using this procedure, the cell bodies and proximal dendrites of identified cholinergic neurons in the neostriatum were found to receive symmetrical synaptic input from substance P-immunoreactive boutons. A similar pattern of substance P-immunoreactive synaptic input was observed onto magnocellular basal forebrain cholinergic neurons in the ventral pallidum and ventromedial globus pallidus. In both the striatum and basal forebrain substance P-immunoreactive boutons were also seen in contact with structures that did not display ChAT immunoreactivity.
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PMID:Substance P-containing terminals in synaptic contact with cholinergic neurons in the neostriatum and basal forebrain: a double immunocytochemical study in the rat. 243 92

The enzyme activities of glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) and concentrations of substance P (SP) and somatostatin were determined in the cerebellum of macaque monkey (Macaca fuscata fuscata) at 3 different ages, embryonic 4 months, embryonic 5.5 months (full-term) and adult. Similar graded increases in the activities of GAD and TH were observed during development. In contrast, ChAT activity was relatively high at embryonic 4 months, increased about twofold between embryonic 4 months and 5.5 months, but did not change between embryonic 5.5 months and adult. These findings suggest that noradrenergic terminals develop synchronously with GABAergic interneurons. On the other hand, the innervation by ChAT-containing fibers is completed during the prenatal period. The concentrations of somatostatin and SP were high at embryonic 4 months, and decreased to, respectively, about 1/18 and 1/4 (expressed per g weight) in adult animals. Several interpretations of the decrease of the two neuropeptides in cerebellar tissue during ontogeny are discussed.
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PMID:Ontogeny of glutamic acid decarboxylase, tyrosine hydroxylase, choline acetyltransferase, somatostatin and substance P in monkey cerebellum. 243 22

A method of perfusion-fixation of the human brain is described and compared with immersion-fixation by immunoperoxidase staining for several substances (tyrosine hydroxylase, substance P, choline acetyltransferase, glutamate decarboxylase, Met-enkephalin, and neuron-specific enolase) in human striatum. Results from 1-cm slices fixed by immersion for 1, 2, 4 and 8 days were compared with results from slices of perfused brain postfixed for the same time periods. The fixative used in all steps was 4% paraformaldehyde at 4 degrees C. In the immersion-fixed brains, optimal immunoreaction for tyrosine hydroxylase and glutamate decarboxylase was limited to a depth of 1-2 mm from the surface of the brain slice. In contrast, staining density in perfusion-fixed brains was relatively homogeneous and of high quality. The other antigens studied displayed more uniform staining throughout the section with both perfused and immersed brains. Investigators intending to study human brain immunohistochemistry using immersion-fixation should be aware of the possibility of depth-related variations in staining intensity and would be wise to determine whether this effect is significant for the antigens they choose to study.
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PMID:Perfusion-fixation of the human brain for immunohistochemistry: comparison with immersion-fixation. 243 8


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