Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The laterodorsal tegmental nucleus (ntdl) contains a cluster of cells located just medial to the locus coeruleus in the pontine brainstem. The ntdl has been shown to project both rostrally to the forebrain and diencephalon and caudally to the spinal cord. In an effort to characterize this region neurochemically, the present study was conducted to identify a variety of neurochemicals localized within perikarya and fibers of the ntdl and surrounding nuclei. Rats were perfused with formalin, and brain sections were processed for fluorescence immunocytochemistry and acetylcholinesterase (AChE). Of the neurochemicals screened, atrial natriuretic factor (ANF), choline acetyltransferase (ChAT), cholecystokinin (CCK), calcitonin gene-related peptide (CGRP), dynorphin B (Dyn B), galanin, somatostatin, substance P, neurotensin (NT), neuropeptide Y (NPY), vasopressin, vasoactive intestinal polypeptide (VIP), serotonin (5HT), glutamic acid decarboxylase (GAD), and tyrosine hydroxylase (TH) were studied. AChE and ChAT staining revealed that the ntdl contains mostly cholinergic neurons. In addition, brightly reactive substance P and galanin and paler staining CRF, ANF, CGRP, NT, VIP, and Dyn B cell bodies were found within the ntdl. Varicose fibers in this nucleus also contained these peptides in addition to CCK, GAD, TH, 5HT, and NPY. The dorsal tegmental nucleus, dorsal raphe nucleus, locus coeruleus, and the parabrachial region contained a dense and varied assortment of peptides with distinct positions and patterns. This multiplicity of neurochemicals within this area suggests a possible influence on a variety of functions modulated by the ntdl and other closely associated tegmental nuclei.
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PMID:Immunocytochemical localization of peptides and other neurochemicals in the rat laterodorsal tegmental nucleus and adjacent area. 289 81

The distribution of neurons and fibres that contain substance P, cholecystokinin-8, vasoactive intestinal polypeptide, corticotropin-releasing factor, calcitonin-gene-related peptide, choline acetyltransferase, tyrosine hydroxylase, somatostatin, leucine-enkephalin, and neuropeptide Y was examined in the parabigeminal nucleus of the rat by immunohistochemistry. Many choline acetyltransferase-like immunoreactive or calcitonin-gene-related peptide-like immunoreactive neurons were observed in the dorsal, middle and ventral subdivisions of the parabigeminal nucleus. A few corticotropin-releasing factor-like immunoreactive neurons were also seen in these three subdivisions. The double-immunostaining demonstrated that some choline acetyltransferase-like immunoreactive neurons in the dorsal and ventral subdivisions contained calcitonin-gene-related peptide. Fibres containing cholecystokinin-8, substance P or vasoactive intestinal polypeptide were abundant in the parabigeminal nucleus. Fibres containing cholecystokinin-8 were concentrated in the dorsal and ventral subdivisions, and the lateral margin of the middle subdivision, whereas many fibres containing substance P or vasoactive intestinal polypeptide existed in the lateral half of each subdivision. Fibres containing calcitonin-gene-related peptide or corticotropin-releasing factor were mostly observed around the immunoreactive neurons. Tyrosine hydroxylase-like immunoreactive fibres were scattered in the parabigeminal nucleus.
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PMID:Localization of neuroactive substances in the rat parabigeminal nucleus: an immunohistochemical study. 290 92

High amplitude spiking representative of seizures, accompanied by an unusual motor behavior pattern of rearing and forelimbic clonus resembling "boxing," was elicited by microinjection of the cholinergic agonist, carbachol, 4 micrograms, into the medial prefrontal cortex of the rat. A rating scale devised to score the behavior revealed a motor pattern elicited by carbachol from the medial anterior cortex which was similar to that described by Racine for electrical stimulation of the amygdala. Topographical analysis of the areas surrounding the medial anterior cortex region revealed that the motor manifestations of seizures were elicited over a wide region of the anterior cortex, with scores significantly lower at carbachol microinjection sites greater than 1 mm rostral, 2 and 3 mm caudal, and 2 mm lateral to the standard medial prefrontal cortex site. Unilateral microinjection of carbachol yielded motor seizures primarily from the contralateral forepaw, suggesting involvement of a crossed pathway. Retrograde tracing with fast blue dye, combined with immunostaining for choline acetyltransferase and NADPH-diaphorase, found that the cholinergic neurons innervating the standard microinjection site were the dorsolateral tegmental cells, as previously reported, which have been shown to also contain substance P and corticotropin releasing factor. In addition, cholinergic neurons of the nucleus basalis of Meynert region were found to innervate the standard microinjection site. These findings implicate cholinergic innervation of the rostral cortex in classical limbic seizures.
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PMID:Anatomical analysis of frontal cortex sites at which carbachol induces motor seizures in the rat. 317 34

Ganglia of the nervus terminalis have been shown to contain luteinizing hormone-releasing hormone (LHRH) immunoreactive cells in several mammalian species. These cells are always accompanied by clusters of cells non-immunoreactive to antiserum to LHRH. Using immunocytochemical procedures, we found choline acetyltransferase (ChAT) and vasoactive intestinal polypeptide (VIP) present in cell bodies and in nerve processes throughout the peripheral, intracranial and central projections of the nervus terminalis. In addition, a dense plexus of substance P (SP) immunoreactive fibers was seen in the nasal mucosa surrounding the nasal glandular acini and blood vessels. A number of SP reactive fibers were traced with the olfactory nerves through the cribriform plate of the ethmoid bone and appeared to enter the brain in the area of the central roots of the nervus terminalis.
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PMID:Localization of choline acetyltransferase and vasoactive intestinal polypeptide-like immunoreactivity in the nervus terminalis of the fetal and neonatal rat. 354 Sep 11

We have previously used organotypic cultures to study mechanisms regulating phenotypic expression of neurotransmitter characters in the brain. Our previous work indicated that nerve growth factor (NGF) specifically increased the activity of choline acetyltransferase (CAT) in striatal cholinergic interneurons. In the present study we examined the effect of NGF on neurons of fetal rat basal forebrain-medial septal area (BF-MS) maintained in organotypic culture. Treatment with 200 biological units/ml of NGF resulted in a 3- to 6-fold increase in the specific activity of CAT. This effect was specifically blocked by anti-NGF antiserum, whereas treatment with antiserum alone did not alter the cholinergic enzyme. NGF also elicited a marked increase in CAT staining intensity, using a monoclonal antibody directed against the enzyme. Further, the number of CAT-positive neurons appeared to increase in the NGF-treated cultures. Exposure to NGF also increased the activity of another cholinergic marker, the catabolic enzyme, acetylcholinesterase. The effect of NGF appeared to be highly selective, since substance P and somatostatin levels were unchanged by NGF treatment.
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PMID:Nerve growth factor selectively increases cholinergic markers but not neuropeptides in rat basal forebrain in culture. 360 70

Antisera to neuropeptide Y (NPY) gave an intense immunohistochemical reaction of certain nerve cells in the myenteric and submucous plexuses of the guinea-pig small intestine. Each nerve cell had up to 20 branching, tapering processes that were less than approximately 50 micron long and a long process that could be followed for a considerable distance. This morphology corresponds to that of the type-III cells of Dogiel. The long process of each myenteric cell ran through the circular muscle to the submucosa, and in most cases the process could be traced to the mucosa. The submucous nerve cell bodies also had processes that extended to the mucosa. These cell bodies, in both plexuses, also stained with antisera raised against calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), choline acetyltransferase (ChAT) and somatostatin (SOM), but did not stain with antibodies against enkephalin, substance P or vasoactive intestinal peptide. Thus, it has been possible for the first time to trace the processes of chemically specified neurons through the layers of the intestinal wall and to show by a direct method that CGRP/CCK/ChAT/NPY/SOM myenteric and submucous nerves cells provide terminals in the mucosa.
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PMID:Neurochemically similar myenteric and submucous neurons directly traced to the mucosa of the small intestine. 383 15

We have examined the effect of the trophic protein, nerve growth factor (NGF), on organotypic cultures of fetal rat striatum. Treatment of cultures with NGF for 10-11 days resulted in a 5- to 12-fold increase in the specific activity of the cholinergic enzyme choline acetyltransferase (CAT; EC 2.3.1.6). in a dose-dependent fashion. This effect was not elicited by insulin, ferritin, or cytochrome c, proteins similar in structure or physicochemical properties to NGF. The effect of NGF on CAT activity was specifically blocked by anti-NGF antiserum, whereas treatment with the antiserum alone did not have a significant effect on the enzyme. Immunocytochemical studies of the treated cultures, using a monoclonal antibody directed against CAT, revealed positively stained neurons exhibiting dendritic and axonal processes. NGF did not have an effect on total protein content of the striatal cultures, suggesting a highly specific effect. Moreover, levels of substance P, a peptide localized to other, noncholinergic neurons, were not altered by NGF. Substance P remained unchanged after treatment with NGF for 12 days, whereas CAT activity increased 12-fold in sister cultures. Although the mechanisms of action of NGF on striatal cholinergic interneurons remain to be determined, the marked, specific response of CAT suggests that this well-defined trophic protein may play a critical role in normal brain development.
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PMID:Nerve growth factor promotes cholinergic development in brain striatal cultures. 386 96

The cholinergic synapses of the rat interpeduncular nucleus (IPN) were demonstrated by immunostaining that utilized a monoclonal antibody directed against choline acetyltransferase. The rostral, central, intermediate and lateral subnuclei of the IPN each contained a single type of immunoreactive terminal. Immunoreactivity was localized to synaptic vesicle membranes (especially at the contact zones), and longitudinal microtubules in preterminal portions of axons. Terminals were identified by comparison to previous studies of the synaptic organization of the IPN. In the rostral subnucleus, the immunoreactive terminals were characterized by their content of spherical vesicles, 45 nm in diameter, intermixed with moderate numbers of dense-cored vesicles, 75-100 nm in diameter. These terminals formed asymmetrical contacts. They correspond to the more numerous of the two types of axodendritic terminals described in this subnucleus, i.e. those which degenerate after lesions of the habenula. The moderate number of immunoreactive terminals in the lateral subnucleus contained pleomorphic vesicles, 30-45 nm in diameter. Up to three of these formed symmetrical contacts with individual dendrites, which ranged in diameter from 0.35 to 0.55 micron. The other types of axodendritic terminal in this subnucleus, which often contacted the same dendrites, were unstained. These latter terminals have been interpreted as being those which contain substance P. The immunoreactive terminals in the diameter, and formed markedly asymmetrical en passant contacts with small dendritic processes or spines. The immunoreactive terminals in the intermediate subnucleus had the same presynaptic and contact morphology. Many were clearly crest synapses. The remainder appeared to be such, but seen only partially within the plane of section. In the intermediate subnucleus there were up to several hundred immunostained terminals per grid square in some sections. These findings are consistent with the existence of a dense cholinergic projection to the IPN. The habenular region, are shown to crest and S synapses, both of which generate after lesions of the cholinergic innervation of other subnuclei of the IPN increases understanding of the relation of cholinergic to other transmitters localized to various portions of this nucleus.
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PMID:Choline acetyltransferase immunoreactivity is localized to four types of synapses in the rat interpeduncular nucleus. 391 48

A major group of cholinergic neurons is present in the midbrain and pontine tegmentum. These cells could be selectively stained using either monoclonal antibodies to choline acetyltransferase, the pharmacohistochemical acetylcholinesterase procedure, or reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry. Using these three techniques, the precise distribution of this cell group was determined. By combining these techniques with immunohistochemical staining for various neuropeptides, examples of peptide-cholinergic coexistence could be demonstrated in this cell group. Approximately 30% of these cholinergic neurons displayed substance P immunoreactivity. Most of these cells also showed corticotropin-releasing factor immunoreactivity and bombesin/gastrin-releasing peptide immunoreactivity. These results therefore provide evidence for the coexistence of various neuropeptides together with NADPH-diaphorase activity in the ascending cholinergic reticular system.
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PMID:Neuropeptides and NADPH-diaphorase activity in the ascending cholinergic reticular system of the rat. 396 Mar 9

The prevalence of severe dementia in the United States is about 1.3 million cases, of which at least 50 to 60% are of the Alzheimer type. Severe dementia of the Alzheimer type is found rarely in a clearly dominant pattern, although often one or more relatives are affected. Down's syndrome in adults is often associated with Alzheimer changes. The diagnosis is a clinicopathological one; there is a considerable error rate in the clinical diagnosis early in the course of the disease, especially in regard to dementia in depression. The differential diagnosis involves a great many disorders, including multi-infarct dementia, tumors, subdural hematomas, and others. Physiological aspects of Alzheimer's disease include a diffusely slow electroencephalogram, reduced cerebral blood flow, and particular patterns noted on positron emission tomographic scanning. The latter technique has also demonstrated that oxygen extraction is normal in Alzheimer's disease, thus excluding ischemia from possible pathogenetic factors. Morphological changes, that is, the presence of plaques and tangles, are widely distributed in neocortex, paleocortex, and many deep gray areas down through the pontine tegmentum, but largely exclude the basal ganglia, thalamus, and substantia nigra. Numerous plaques without neocortical tangles are found in many demented persons older than 75 years. A severe loss of large neocortical neurons is characteristic of the disease. The chemical nature of the paired helical filaments that make up the neurofibrillary tangle has not yet been ascertained. Neurons are markedly deficient in the basal forebrain nuclei, and this deficiency may account for the severe diminution of choline acetyltransferase and acetylcholine in the neocortex and paleocortex. Muscarinic cholinergic receptors are present in normal amounts. Norepinephrine is reduced in some cases, and somatostatin in most. Substance P is low in severe cases. The etiology of the disorder is unknown and the role of aluminum is disputed. Management of patients with Alzheimer's disease is difficult, and neuroleptics are to be used with great caution because of their side effects. Substrate therapy has not been effective; physostigmine improves memory but is not suitable for general use. Trophic factors, gangliosides, and aluminum chelation are being investigated for use in pharmacological intervention.
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PMID:Senile dementia of the Alzheimer type. 613 75


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