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 ultrastructural localization and relations of substance P- and met-enkephalin-labeled neuronal structures were examined in the wall of the human gastric antrum during early fetal life. By 14-16 weeks of gestation, clearly discernable neural plexuses and a well developed external muscle coat were present. In the submucous coat, neural plexuses varied from immature forms consisting of 1-4 neurites partially enveloped by Schwann cell processes to more mature plexuses where neurons were completely enclosed by Schwann cell processes. Neuronal profiles with substance P- and met-enkephalin-like immunoreactivities were observed in the submucous plexus. In the myenteric plexus met-enkephalin-like immunoreactivity was seen within cell bodies and neurites. By contrast, although substance P-like immunoreactivity was observed in neurites in the myenteric plexus, no substance P-labeled somata could be identified. Unlabeled terminals were seen in contact with both unlabeled dendrites and met-enkephalinergic neurons. An increase in electron density was observed at the sites of contact. These structures probably represent early stages in the development of synaptic specializations. In addition, met-enkephalin-labeled varicosities were seen in apposition to smooth muscle cells of the circular muscle coat. This suggests that antral smooth muscle cells are directly innervated by met-enkephalin neurons.
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PMID:Ultrastructure and localization of substance P and met-enkephalin immunoreactivity in the human fetal gastric antrum. 241 74

Experiments were designed to identify the neural cell type(s) responsible for the aromatization and 5 alpha-reduction of androgens in the rat hypothalamus. Primary cultures of fetal rat hypothalamic cells, which had enhanced neuronal morphology, were treated at various times after plating with kainic acid (KA), a neurotoxic agent which selectively destroys neuronal cells. Neuronal morphology was disrupted in a time (0-6 days)- and dose (10(-4)-10(-2) M)-dependent fashion after KA treatment, with no apparent change in the appearance of the flattened, underlying non-neuronal cells. KA treatment for 4 days decreased aromatization by 94% in a dose-dependent fashion (10(-4)-10(-2) M KA), while 5 alpha-reduction declined by no more than 25%. A 6-day time course with 10(-3) M KA showed a dramatic decline in aromatization and no alteration in 5 alpha-reduction. In control experiments, substance P, a neuronal peptide, declined after KA treatment while the activity of glutamine synthetase, a glial enzyme, did not change. We conclude from these results that aromatase is localized primarily to neuronal cells in the hypothalamus while 5 alpha-reductase is confined primarily to non-neuronal cells.
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PMID:Localization of aromatase and 5 alpha-reductase to neuronal and non-neuronal cells in the fetal rat hypothalamus. 242 95

Sensory transmission from the colon was studied using a preparation of inferior mesenteric ganglion (i.m.g.) attached to a segment of distal colon in guinea-pigs, in vitro. Electrical responses to colon distension were recorded intracellularly from neurones of the i.m.g. Distension of the distal colon up to an intraluminal pressure of 20 cmH2O caused an increase in resting asynchronous synaptic activity and a concomitant slow depolarization. The asynchronous synaptic activity, but not the slow depolarization, was abolished by cholinergic antagonists. Distension-induced non-cholinergic depolarizations were elicited in 44% of i.m.g. neurons sampled. For distensions of 1 min at 10-20 cmH2O, depolarizations reached a mean amplitude of 3.4 +/- 0.3 mV and lasted 108 +/- 7 s. Continuous distension resulted in a tachyphylaxis of the depolarization. Tetrodotoxin (3 X 10(-7) M) superfused over the i.m.g. reversibly abolished the distension-induced non-cholinergic depolarization. Distension-induced non-cholinergic depolarizations were accompanied by an increase in input resistance of 21%. Neuronal excitability also increased, as sub-threshold potentials produced by intracellular current injection reached threshold for firing action potentials during colon distension. The amplitude of non-cholinergic depolarizations increased with colonic intraluminal pressure between 2 and 20 cmH2O, although the slope of the mean amplitude-pressure curve decreased progressively at higher pressures. The amplitude of distension-induced non-cholinergic depolarizations increased as membrane potential was manually hyperpolarized to approximately -80 mV, whereupon further hyperpolarization resulted in a decrease in response amplitude. Non-cholinergic slow excitatory post-synaptic potentials (e.p.s.p.s) evoked by repetitive presynaptic nerve stimulation were reversibly attenuated by 19 +/- 8% during depolarizations produced by distension. Systemic administration of capsaicin (50-350 mg/kg) reduced the number of i.m.g. neurones exhibiting the non-cholinergic mechanosensory response; direct superfusion of capsaicin over the i.m.g. attenuated the response in some neurones but had no effect in others. These results demonstrate the existence of a non-cholinergic mechanosensory pathway from the colon to the i.m.g., and suggest that non-cholinergic transmission in the ganglion participates in mediating gastrointestinal reflexes. One transmitter utilized by the non-cholinergic mechanosensory pathway may be substance P.
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PMID:Non-cholinergic transmission in a sympathetic ganglion of the guinea-pig elicited by colon distension. 242 4

Restricted numbers of substance P-like-immunoreactive (SPL-IR) neurons were demonstrated in the photosensory pineal organ of the rainbow trout. The small parapineal organ of this teleost species receives a distinct SPL-IR innervation via the habenular nuclei, but displays no intrinsic SPL-IR neurons. Intrapineal SPL-IR neurons were located in the rostral portion of the pineal end-vesicle. Neuronal somata were found in a lateral position with smooth axonal processes extending mediad. Immunoreactive somata and axonal processes were observed intraparenchymally as well as in the pineal lumen. The pattern of immunoreactivity was not changed in excised pineal organs that had been incubated in tissue culture medium in the dark for 18 h. The possibility that the intrapineal SPL-IR neurons are not part of the neural circuitry involved in the transduction of photic information, but may have other functions, is discussed.
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PMID:Substance P-like-immunoreactive neurons in the photosensory pineal organ of the rainbow trout, Salmo gairdneri Richardson (Teleostei). 243 Jul 18

Experiments reported in this study have been performed in order to investigate cholinergic and GABA-ergic neurotransmitter systems and substance P in the realization of internal inhibition and pain reinforcement. This was accomplished during the elaboration of inhibitory and defensive conditioned reflexes to light flashes in alert, nonimmobilized rabbits. Present results together with a review of past research indicate that the cholinergic system is directly involved in transmitting the effects of pain reinforcement to neocortical neurons. Substance P, a neuropeptide, reduces the background activity of neocortical and hippocampal neurons and the response of cortical neurons to pain and positive conditioned stimuli. The cholinergic system and substance P exert a modulating effect on the elaboration of internal inhibition. Phenybut, a GABA derivative capable of penetrating the blood-brain barrier, enhances inhibitory hyperpolarization in the cerebral cortex and improves discrimination between the inhibitory and reinforcing light flashes. It appears, therefore, that the GABA-ergic system plays a leading part in the elaboration of internal inhibition. Neuronal activity and slow potential changes in response to positive conditioned and pain stimuli occur in the same direction after administering the preparations, and the dynamics of these changes is different from that in responses to inhibitory stimuli. It may be supposed on these grounds that the neurotransmitter and neuromodulator systems studied possess a considerable degree of plasticity.
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PMID:On neurotransmitter mechanisms of reinforcement and internal inhibition. 243 77

Neural crest, taken from cephalic and trunk levels of quail embryos, was grown in vitro in conventional tissue culture medium (Dulbecco's modified Eagle's medium containing 15% fetal calf serum and either 2 or 15% chick embryo extract (CEE] or in a chemically defined serum- and CEE-free medium. Depending on the conditions employed, different types of neuronal or neuronlike cells developed in the cultures. Thus, in medium containing 15% CEE, adrenergic cells (identified by tyrosine hydroxylase immunoreactivity and catecholamine histofluorescence) emerged after 5-6 days. These cells lacked tetanus toxin binding sites and did not react with an antibody directed against 70-kDa neurofilament protein. In the fully defined medium, a neuronal cell type exhibiting neurofilament and substance P (SP) immunoreactivity differentiated from noncycling precursors within 1 or 2 days of culture. If serum was added to the medium, the neurites disintegrated and the neuronal cells ultimately died. By sequentially culturing neural crest, first in the wholly synthetic medium for 1-3 days and then in the conventional medium supplemented with serum and 15% CEE, the disappearance of the SP-positive neurons was followed, several days later, by the emergence of adrenergic cells. The majority of these cells and/or their precursors were found to undergo cell division in culture. We conclude that the cells expressing the adrenergic phenotype (characteristic of the sympathetic nervous system) and those displaying SP immunoreactivity, comparable to a category of neurons in dorsal root and cranial sensory ganglia, derive from distinct sets of precursors. Our results reinforce the contention, deduced from in ovo transplantation experiments (see N. M. Le Douarin, (1984) In Cellular and Molecular Biology of Neuronal Development (I. Black, Ed.), pp. 3-28. Plenum, New York), that at least two lineages, from which sensory and autonomic cell types are derived respectively, are segregated early during neural crest ontogeny and have extremely different survival and trophic requirements.
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PMID:Cell lineages in peripheral nervous system ontogeny: medium-induced modulation of neuronal phenotypic expression in neural crest cell cultures. 243 74

Neuronal precursor cells present in dorsal root ganglia (DRG) during early development have been previously shown to differentiate in vitro to neurons, as characterized by morphology, cell surface antigens, and electrophysiological properties (H. Rohrer, S. Henke-Fahle, T. El-Sharkawy, H. D. Lux, and H. Thoenen, 1985, Embo J. 4, 1709-1714). In the present study the conditions necessary for the initial differentiation and long-term survival of these cells were established, and the neurotransmitter phenotype of the newly differentiated neurons was analyzed. Neuronal precursor cells isolated from chick DRG at Embryonic Day 6 (E6) were found to require the presence of a polyornithine substrate coated with either laminin or fibronectin for initial neurite production and long-term survival. Neurons were unable to develop on polyornithine alone or on polyornithine coated with BSA. The survival and neurite outgrowth from neuronal precursor cells was not affected by the presence of nerve growth factor (NGF) during the first 9 hr in culture. NGF also had no effect on the proportion of cells expressing the neuron-specific Q211 antigen. However, after this initial differentiation period the neurons did require the presence of a survival factor. The neurons could be maintained for at least 6 days in culture both in the presence of NGF and in the presence of brain-derived neurotrophic factor (BDNF). At saturating concentrations of both survival factors no additive effects could be observed, indicating a complete overlap of NGF- and BDNF-responsiveness. Although the same proportion of cells survived with either NGF or BDNF during the first 3 days in culture, survival decreased in the presence of BDNF but not in the presence of NGF during the following 3 days in culture. The loss of BDNF responsiveness in vitro was also observed in vivo. After 6 days in culture about 70% of the neurons expressed substance P immunoreactivity, and approximately the same proportion was positive for myelin-associated glycoprotein immunoreactivity. The neurons did not express properties of adrenergic neurons such as tyrosine hydroxylase immunoreactivity or norepinephrine uptake. These findings indicate that the neuronal precursor cells from E6 DRG acquire the same characteristics in vitro as in their normal in vivo environment.
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PMID:Neuronal precursor cells in chick dorsal root ganglia: differentiation and survival in vitro. 245 Jul 97

Using an autoradiographic receptor binding technique, the distribution of substance P (SP) receptors on cells cultured from the superior cervical ganglia (SCG) of newborn rats was investigated. Binding sites for 125I-Bolton-Hunter-SP were observed on a subpopulation of 35-50% of the ganglion neurones. The percentage of labelled neurones remained constant whether the cultures were seeded densely or sparsely. Variation in the density of labelling was observed on different neuronal clusters. Neuronal cell bodies were often densely labelled, but neuronal processes were rarely labelled. In contrast with the neuronal cells, specific labelling was not associated with other cell types found in this culture preparation, including fibroblasts, glial cells and other non-neuronal supporting cells. These results are interpreted to suggest that there is a subpopulation of SCG neurones which, by virtue of their expressing SP receptors, are responsive to SP and have a physiological role within the ganglion.
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PMID:Autoradiographic localization of binding sites for 125I-substance P on neurones from cultured rat superior cervical ganglion. 246 45

The cellular components of striatal grafts into the host striatum of rats were studied using [3H]thymidine autoradiography, histochemistry, immunocytochemistry and Golgi-staining. Autoradiography revealed that a layer of glial cells, somas smaller than 8 microns in diameter, stained positive with glial fibrillary acidic protein, and demarcating transplant from host, is derived mainly from the donor. Golgi studies revealed that many neuronal fibers fail to cross the glial layer to reach the host striatum. Migration of transplanted striatal cells into the host milieu was evident. The density of migrated cells decreased linearly as a function of distance from the transplant. Most of the far-migrated cells were glial cells. Neuronal migration was limited. In the transplant, donor cells marked by [3H]thymidine constituted at least 70% of the population. Neurons which stained positively for GABA, substance P, and acetylcholinesterase were identified in the transplant. Fibers of two of these three neuronal types, substance P and acetylcholinesterase, formed patchy patterns in the transplant. Detailed morphology on GABAergic fiber is not available to date, because of the limited antibodies or the method used. GABA is the highest population in the striatal transplant. Two types of GABA-positive cells were clearly distinguishable according to cell size. A majority resembled the medium-sized cell commonly found in striatum, while those of the other type resembled the larger GABA cells usually found in the globus pallidus.
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PMID:Neuronal and glial elements of fetal neostriatal grafts in the adult neostriatum. 247 10

Cell membrane contact induces marked differential changes in neurotransmitter expression. In cultures of virtually pure dissociated sympathetic neurons, when such contact is provided by either high cell densities or addition of membranes derived from specific tissues, there is a marked increase in cell-specific content of substance P and de novo induction of choline acetyltransferase. To identify molecular mechanisms underlying regulation of transmitter expression by neuronal aggregation and membrane contact, we have begun to isolate and characterize a membrane-associated factor responsible for stimulation of choline acetyltransferase activity. The factor was found in substantial quantities in membranes from adult rat spinal cord as well as from sympathetic and sensory ganglia. Ionic mechanisms were employed to extract transmitter-inducing activity from spinal cord membranes in soluble form. The solubilized factor was then partially purified by ion exchange and gel filtration chromatography. It appears to be an extrinsic (non-integral) protein with an apparent molecular weight of 27. It is inactivated by trypsin and chymotrypsin, but is only moderately sensitive to heat inactivation, retaining activity at 60 degrees C but not at 90 degrees C. Neuronal perikaryal contact via aggregation represents a critical mechanism by which neurons themselves may influence phenotypic expression. Membrane localization of the factor provides a means by which cell contact may regulate transmitter expression.
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PMID:Neuronal aggregation and neurotransmitter regulation: partial purification and characterization of a membrane-derived factor. 281 89


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