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)

Host afferents into fetal ventral mesencephalic tissue grafted to the neostriatum of adult rats have been studied by using anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and immunocytochemistry for serotonin (5-HT), Substance P (SP), and dopamine-adenosine 3':5'-monophosphate-regulated-phosphoprotein-32 (DARPP-32). Numerous fibers of cortical origin were detected in the transplants following multiple (11-15) iontophoretic injections of PHA-L into the frontal and anterior cingulate cortex. The labeled fibers occurred with an apparently random distribution throughout the graft tissue. Their overall density was lower than that of the surrounding striatum but similar to that found in the host nigra-ventral tegmental area. The majority of the PHA-L-labeled fibers in the grafts were thin and tortuous with varicosities or lateral clubs with terminal boutons. Dual labeling showed frequent close appositions between PHA-L-labeled terminals and dopamine-immunoreactive cell bodies. In parallel electron microscopy, synaptic contacts were observed between PHA-L-labeled terminals and unlabeled neuronal profiles in the graft. Other labeled fibers in the grafts were thick and smooth, corresponding probably to labeled myelinated axons observed in the electron microscope. These thick fibers were often seen to give off collaterals of the thin type. The virtual absence of such thick fibers in the normal striatal neuropil suggests that at least some of the cortical afferents to the grafts may have sprouted from axons normally projecting to diencephalic or brain stem regions. Serotonin fibers occurred in patches or as scattered single fibers in both deep and superficial portions of the nigral transplants. In the electron microscope some of these terminals were seen to establish synaptic contacts with nonimmunoreactive elements in the graft. These fibers were present also when the graft tissue had been pretreated with 5,7-dihydroxytryptamine at the time of transplantation. This treatment eliminated all 5-HT-containing neurons from the grafts without any noticeable adverse effect on the survival of the dopaminergic neurons. The serotonin fibers in the grafts were thus most likely of host origin. SP-positive fibers formed a dense plexus inside the grafts. Since many SP-positive cell bodies were visualized inside the transplant after colchicine pretreatment, it is unclear, however, whether any of these fibers were of host origin. Intrastriatal injections of PHA-L or DARPP-32 immunocytochemistry indicated that the deep portions of the nigral grafts were entirely devoid of host striatal afferents.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Host afferents into intrastriatal transplants of fetal ventral mesencephalon. 247 71

In the present experiment we attempted to confirm the specific stimulation of substance P (SP) on human T lymphocyte proliferation as reported by Payan et al. and to observe its effect on human B lymphocyte proliferation. As a result, no definite mitogenic effect of SP (10(-11) to 10(-7) M) was found on both human T and B cells, no significant influence of SP on the blastogenic response of T cells to Con A or PHA stimulation in a wide range of concentrations and no effect on proliferative response of B cells to Staphylococcus aureus Cowen strain I stimulation were shown. Payan's conclusion was based on percentage increase of 3H-TdR incorporation. But as the background cpm is generally very low, even 100 per cent increase would only indicate a very small cpm increase, so in this situation percentage increase might give false phenomenon, and only cpm could tell whether the effect was strong or weak. Thus, we believe that is the reason for our disagreement with Payan's conclusion.
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PMID:Observation of the effect of substance P on human T and B lymphocyte proliferation. 608 76

Substance P (SP) and SP(4-11) stimulated significantly the proliferation of human T lymphocytes in vitro at respective concentrations of 10(-11) M to 10(-7) M and 10(-9) M to 10(-7) M, as assessed by the uptake of [3H]thymidine and [3H]leucine. The proliferative response of human T lymphocytes to PHA was augmented by 10(-9) M to 10(-8) M SP and 10(-10) M to 10(-7) M SP(4-11). The inactive analogue [D-Pro2, D-Phe7, D-Trp9]-SP inhibited the effects of SP on T lymphocytes. The specific stimulation of T lymphocytes by SP suggests a unique mechanism for the regulation of immunologic responses by peripheral nerve-derived factors.
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PMID:Specific stimulation of human T lymphocytes by substance P. 619 7

The neuropeptide substance P (SP) has been shown to play an important role as a mediator of neurogenic inflammation. Moreover, in vitro SP is capable of modulating the activity of lymphocytes, monocytes and polymorphonuclear cells. We have examined one of the early events that occur after addition of SP to human peripheral blood mononuclear cells (PBMC). Addition of 10(-6)-10(-4) M SP to human peripheral blood mononuclear cells results in a dose-dependent rise in intracellular calcium concentration as determined by FACS analysis. We show that the effect of SP cannot be attenuated by the SP receptor antagonist [D-Pro4,D-Trp7,9]-SP(4-11), indicating that the response is not mediated via a SP receptor. Amphiphilic peptides like SP appear to have the capacity to insert themselves into the cell membrane and interact directly with intracellular proteins. This hypothesis is supported by the fact that the amphiphilic analogue of SP, [D-Pro2,D-Phe7,D-Trp9]-SP, is capable of inducing a calcium response in our system, although it is known as an SP receptor antagonist. Functionally, we show that SP increases the proliferative response of T cells induced by suboptimal concentrations of the mitogen PHA. These data provide evidence of a potential role of SP in the regulation of lymphocyte activation.
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PMID:Substance P induces a rise in intracellular calcium concentration in human T lymphocytes in vitro: evidence of a receptor-independent mechanism. 767 98

The efferent connections of the rostral pole of the rat accumbens, where distinct core and shell subterritories can not be identified, were examined with the aid of the anterogradely transported plant lectin, Phaseolus vulgaris-leucoagglutinin (PHA-L), for comparison with the previously reported projection patterns of the accumbal core and shell. Injection sites and transported PHA-L were evaluated with the aid of reference to adjacent sections processed to display substance P or calbindin 28 kD immunoreactivities, i.e., markers that demonstrate the core and shell. Lateral parts of the rostral pole gave rise to a "core-like" projection system that involved the rostroventral globus pallidus, subcommissural ventral pallidum, entopeduncular nucleus and an adjacent part of the lateral hypothalamus, lateral ventral tegmental area, dorsal pars compacta, and structures in the lateral mesencephalic tegmentum and central grey. The medial part of the rostral pole gave rise to a "shell-like" innervation of the subcommissural ventral pallidum, lateral preoptic region, lateral hypothalamus, ventral tegmental area, dorsalmost pars compacta, retrorubral field, lateral midbrain tegmentum, and central grey. In contrast to the large numbers of axon varicosities observed through the entire length of lateral hypothalamus following shell injections, dense accumulations of axon collaterals and varicosities in hypothalamus were limited to the levels of origin of the stria medullaris bundle and entopeduncular nucleus and to the posterlateral region following medial injections. The medial part of the rostral pole contributed some projections to preoptic and sublenticular regions, but not to the bed nucleus of the stria terminalis. Noteworthy concentrations of calbindin immunoreactive cells observed in the lateral rostral pole correlate with the origin of the "basal ganglia-like" projection system, provoking the speculation that ventral striatal calbindin immunoreactive cells contribute principally to basal ganglia-like projections while cells lacking calbindin immunoreactivity contribute to the innervation of hypothalamus and midbrain tegmentum.
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PMID:Specificity in the efferent projections of the nucleus accumbens in the rat: comparison of the rostral pole projection patterns with those of the core and shell. 842 43

The anterograde neuronal tracing properties of Fluoro-Gold (FG) were characterized in this study by its ability to label the retinohypothalamic tract (RHT) upon pressure injection of the substance into the vitrous body of the eye in the Djungarian hamster, Phodopus sungorus. Tracing was compared to the anterograde neuronal transport of cholera toxin B subunit (CTB), Fast blue (FB), Phaseolous vulgaris leucoagglutinin (PHA-L) and biocytin. After survival times that ranged from 24 h to 4 weeks, a major projection was found to the bilateral hypothalamic suprachiasmatic nuclei (SCN). Labeling was also found in the anterior medial preoptic nucleus and, in relatively sparse amounts, in the lateral geniculate nucleus, superior colliculus and lateral habenular nucleus. Similar results were obtained upon injection of CTB or FB, respectively, into the eye, whereas the application of PHA-L or biocytin did not label retinal afferents. The combined injection of FG and CTB or FB into the same eye labeled retino-afferent fibers only when FG was applied three days before the injection of the other tracers. Retrogradely labelled neurons were sen occasionally in the hypothalamus which may provide a sparse retinopetal projection. Additional experiments combining FG tracing and the immunofluorescent detection of the neuropeptides substance P (SP) or vasoactive intestinal polypeptide (VIP) in the SCN showed that FG-containing punctae were accumulated in the vicinity of immunoreactive cell bodies. Our data demonstrate that FG may be used as an anterograde axonal tracer of the retinohypothalamic pathway.
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PMID:Anterograde tracing of retinohypothalamic afferents with Fluoro-Gold. 903 10

Cholinergic interneurons are the only known source of acetylcholine in the rat nucleus accumbens (nAcb); yet there is little anatomical data about their mode of innervation and the origin of their excitatory drive. We characterized the cholinergic and thalamic innervations of nAcb with choline acetyltransferase (ChAT) immunocytochemistry and anterograde transport of Phaseolus vulgaris-leucoagglutinin (PHA-L) from the midline/intralaminar/paraventricular thalamic nuclei. The use of a monoclonal ChAT antiserum against whole rat ChAT protein allowed for an optimal visualization of the small dendritic branches and fine varicose axons of cholinergic interneurons. PHA-L-labeled thalamic afferents were heterogeneously distributed throughout the core and shell regions of nAcb, overlapping regionally with cholinergic somata and dendrites. At the ultrastructural level, several hundred single-section profiles of PHA-L and ChAT-labeled axon terminals were analyzed for morphology, synaptic frequency, and the nature of their synaptic targets. The cholinergic profiles were small and apposed to various neuronal elements, but rarely exhibited a synaptic membrane specialization (5% in single ultrathin sections). Stereological extrapolation indicated that less than 15% of these cholinergic varicosities were synaptic. The PHA-L-labeled profiles were comparatively large and often synaptic (37% in single ultrathin sections), making asymmetrical contacts primarily with dendritic spines (>90%). Stereological extrapolation indicated that all PHA-L-labeled terminals were synaptic. In double-labeled material, some PHA-L-labeled terminals were directly apposed to ChAT-labeled somata or dendrites, but synapses were never seen between the two types of elements. These observations demonstrate that the cholinergic innervation of rat nAcb is largely asynaptic. They confirm that the afferents from midline/intralaminar/paraventricular thalamic nuclei to rat nAcb synapse mostly on dendritic spines, presumably of medium spiny neurons, and suggest that the excitatory drive of nAcb cholinergic interneurons from thalamus is indirect, either via substance P release from recurrent collaterals of medium spiny neurons and/or by extrasynaptic diffusion of glutamate.
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PMID:Cholinergic innervation and thalamic input in rat nucleus accumbens. 1877 52


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