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)

P-type, E-type, and K-type tachykinin binding sites have been identified in the mammalian CNS. These sites may be tachykinin receptors for which the mammalian neuropeptides substance P, neuromedin K, and substance K are the preferred natural agonists, respectively. In the present investigation, we have compared the pharmacology and the autoradiographic distribution of CNS binding sites for the iodinated (125I-Bolton-Hunter reagent) tachykinins substance P, eledoisin, neuromedin K, and substance K. Iodinated eledoisin and neuromedin K exhibited an E-type binding pattern in cortical membranes. Iodinated eledoisin, neuromedin K, and substance K each labeled sites that had a similar distribution but one that was considerably different from that of sites labeled by iodinated substance P. CNS regions where there were detectable densities of binding sites for iodinated eledoisin, neuromedin K, and substance K and few or no sites for iodinated substance P included cortical layers IV-VI, mediolateral septum, supraoptic and paraventricular nuclei, interpeduncular nucleus, ventral tegmental area, and substantia nigra pars compacta. Binding sites for SP were generally more widespread in the CNS. CNS regions where there was a substantial density of binding sites for iodinated substance P and few or no sites for iodinated eledoisin, neuromedin K, and substance K included cortical layers I and II, olfactory tubercle, nucleus accumbens, caudate-putamen, globus pallidus, medial and lateral septum, endopiriform nucleus, rostral thalamus, medial and lateral preoptic nuclei, arcuate nucleus, dorsal raphe nucleus, dorsal parabrachial nucleus, parabigeminal nucleus, cerebellum, inferior olive, nucleus ambiguus, retrofacial and reticular nuclei, and spinal cord autonomic and somatic motor nuclei. In the brainstem, iodinated substance P labeled sites in both sensory and motor nuclei whereas iodinated eledoisin, neuromedin K, and substance K labeled primarily sensory nuclei. Our results are consistent with either of two alternatives: (1) that iodinated eledoisin, neuromedin K, and substance K bind to the same receptor site in the rat CNS, or (2) that they bind to multiple types of receptor sites with very similar distribution.
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PMID:Pharmacologic characterization and autoradiographic distribution of binding sites for iodinated tachykinins in the rat central nervous system. 303 29

Endopeptidase-24.11, a plasma membrane ectoenzyme with the ability to hydrolyse a variety of neuropeptides, has been localized in the pig nervous system by an immunoperoxidase technique. The endopeptidase was mapped in cryostat sections of the fore and mid-brain to the following structures: caudate-putamen, globus pallidus, olfactory tubercle, nucleus interpeduncularis and substantia nigra. Endopeptidase-24.11-like immunoreactivity was also found in the pia mater, choroid plexus and ependymal lining of the central canal. In the spinal cord, weak staining was observed in the dorsal horn, but strong staining was found in the dorsal root ganglia and nerve roots. Within the central nervous system, endopeptidase immunoreactivity was confined to gray matter and within the positive areas of the striatum densely staining areas, corresponding to striosomes, were discernible. These well-defined structures were exploited in serial sections to examine the alignment of the enzyme-rich patches of neuropil with correspondingly strong staining for other antigens. A consistent match was observed with a monoclonal antibody to neurofilament protein, but there was a poor correlation with a polyclonal antibody to glial fibrillary acidic protein. Substance P-like and [Leu]enkephalin-like immunoreactivity were also studied in sections adjacent to those stained for the endopeptidase. Good matching between enzyme-rich and peptide-rich areas was observed, but some enkephalin-rich areas did not align with enzyme staining and indeed endopeptidase-rich areas were not necessarily matched with areas rich in either peptide. These findings suggest a neuronal rather than an astrocytic location for endopeptidase-24.11 in the CNS and lend support to the view that it plays a central role in neuropeptide metabolism at membrane surfaces. In the peripheral nervous system, the endopeptidase was located in Schwann cell membranes surrounding dorsal root ganglion cells and nerve fibres, while in the pituitary the main concentration was in the adenohypophysis, where only a proportion of the endocrine cells were found to be immunoreactive.
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PMID:An immunohistochemical study of endopeptidase-24.11 ("enkephalinase") in the pig nervous system. 309 17

The distribution of FMRFamidelike peptides was studied in the nervous system of the lobster Homarus americanus by using immunocytochemical and radioimmunological techniques. By radioimmunoassay FMRFamidelike immunoreactivity (FLI) was found in low levels (ca. 1 pmol/mg protein) throughout the ventral nerve cord and in much higher amounts (60-100 pmol/mg protein) in the neurosecretory pericardial organs. Immunocytochemical studies showed FLI in approximately 300-350 cell bodies, and in distinct neuropil regions, neuronal fiber tracts, and varicose endings. Specificity of the immunostaining was tested by preabsorbing the antiserum with FMRFamide, with peptides having similar carboxyl termini to FMRFamide (Met-enkephalin-Arg-Phe, Phe-Met-Arg-Tyr-amide), with several amidated peptides (alpha-melanocyte-stimulating hormone, substance P, oxytocin), and with proctolin, a peptide found widely distributed in the lobster nervous system. Of these substances, only FMRFamide blocked the staining. In addition to the pericardial organs, significant levels of FLI were found in neurosecretory regions associated with thoracic second roots and in the connective tissue sheath that surrounds the ventral nerve cord. In all three regions, immunocytochemical studies showed the FLI to be localized to fine fibers and associated terminal varicosities lying close to the surface of the tissue, with no obvious target in their immediate vicinity. When examined at the ultrastructural level, the immunoreactive varicosities of the thoracic second roots and of the ventral nerve cord sheaths were found a few microns from the surface of the tissue and contained electron-dense granules. In the immunoreactive nerve cord sheath endings, in addition to the large, dense granules, small, clear vesicles were found. The appearance and location of these terminals suggest a neurohormonal role for FMRFamidelike peptides in lobsters. The observation that low levels of FLI are found in the hemolymph supports this suggestion. In addition, the localization of FLI to particular neuronal somata, fiber tracts, and neuropil regions suggests possible functional roles for these peptides in (1) integration of visual and olfactory information, (2) function of the anterior and posterior gut, and (3) the control of exoskeletal muscles.
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PMID:FMRFamidelike peptides of Homarus americanus: distribution, immunocytochemical mapping, and ultrastructural localization in terminal varicosities. 332 67

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

Substance P (SP) is a putative neurotransmitter in both the peripheral and central nervous systems. In the present report we have used a modification of the Young and Kuhar technique to investigate some of the SP receptors binding properties and the distribution of SP receptors in rat brain. Tritiated SP [( 3H]SP) absorbed extensively to glass but this adsorbtion was greatly reduced by preincubating the slide-mounted tissue sections in a solution containing the cationic polymer polyethylenimine. [3H]SP was found to bind to rat tissue in a saturable fashion with a Bmax of 14.7 fmol/mg tissue wet weight and a Kd of 1.1 nM. The rank order of potencies for displacing [3H]SP binding from rat tissue sections was SP greater than SP sulphoxide greater than DiMeC7 greater than Eledoisin greater than SP(5-11) greater than SP(COOH) greater than SP(1-9) amide. Using autoradiography coupled with LKB tritium-sensitive Ultrofilm or the dry emulsion-coated coverslip technique the distribution of [3H]SP binding sites was found to be very dense within olfactory bulb, amygdalo-hippocampal area and the nucleus of the solitary tract. Heavy concentrations of receptors were observed in the septum, diagonal band of Broca, striatum subiculum, hypothalamus, locus coeruleus, parabrachial nucleus and lobule 9 and 10 of the cerebellum. Moderate to low concentrations of receptors were observed in the cerebral cortex, globus pallidus, raphe nuclei and the trigeminal nucleus. Very low densities were observed in most aspects of the dorsal thalamus, substantia nigra and cerebellum (other than lobule 9 and 10). Comparisons of the present data with SP peptide levels indicate that in some areas of the brain there is a rough correlation between peptide and receptor levels. However, in other brain areas (olfactory bulb, globus pallidus and substantia nigra) there is little obvious correlation between the two.
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PMID:Substance P receptors: localization by light microscopic autoradiography in rat brain using [3H]SP as the radioligand. 608 84

The characteristics of the islands of Calleja complex (ICC) in the basal forebrain of the rat were studied with immunohistochemistry, histofluorescence, acetylcholinesterase staining, India ink vascular perfusions, electron microscopy, and steroid autoradiography. The ICC contains clusters of granule cells and associated medium-sized and large cells in the surrounding neuropil of the olfactory tubercle and septum-nucleus accumbens interface. The ICCs were found to contain monoamine fibers (dopamine and norepinephrine), neuroactive peptide fibers (leu-enkephalin, met-enkephalin, substance P, cholecystokinin, luteinizing hormone-releasing hormone), acetylcholinesterase-containing somata and dendrites, and medium-sized and large cells that concentrate [3H] estradiol. The specific overlap and combination of putative neurotransmitters in separate compartments of the ICC suggest that these structures contain striatum- and pallidumlike components. Striatumlike regions are defined as the zone in the rim regions of the ICC and are innervated predominantly by dopamine and cholecystokinin inputs. Pallidumlike regions are defined as the synaptic zone near the medium-sized and large cells of the cap and core regions of the ICC and they are innervated predominantly by enkephalin, substance P, and gamma aminobutyric acid inputs. The morphology, connections, and neurotransmitter relationships of the ICC, therefore, resemble classical striatopallidal systems. The additional presence of substances involved in the reproductive neuroendocrine systems (luteinizing hormone-releasing hormone, estradiol-binding cells, especially in the medial ICC, suggest that some ICC are involved in an endocrine corticostriatopallidal system. These endocrine systems resemble other neocortically and allocortically originating corticostriatopallidal systems in terms of their cell types, connections, and neurotransmitter systems. A functional role for the ICC in extrapyramidal motor systems is proposed.
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PMID:The islands of Calleja complex of rat basal forebrain. III. Histochemical evidence for a striatopallidal system. 613 33

A number of in vitro preparations of the central nervous system have been used to characterize with intracellular recording the cellular actions of four neuropeptides. Carnosine, the putative excitatory neurotransmitter of olfactory nerves, was found to exert little or no effect in the turtle or the frog olfactory bulb, suggesting that this peptide may have other roles, e.g. neurotropic, in this system. Substance P and TRH were found to have some characteristics of a classical excitatory transmitter since they increase membrane conductance and depolarize frog motoneurons by a direct action. However, the slow time course and subthreshold nature of the depolarization may imply that these peptides function in a background manner to set the level of excitability of motoneurons. Finally, the effects of enkephalin on a variety of inhibitory systems have been examined. Enkephalin excites hippocampal pyramidal cells indirectly by blocking both spontaneous and evoked inhibitory potentials. In addition, both feedforward and feedback inhibitory pathways are depressed by enkephalin. All these effects are blocked by naloxone. Blockade of inhibitory pathways by enkephalin appears to be a general phenomenon, since similar depressant effects were seen for dendrodendritic inhibition in olfactory bulb mitral cells as well as for presynaptic inhibition of spinal primary afferents. These results indicate that neuroactive peptides can affect principal neurons by increasing their excitability via either subthreshold excitation or disinhibition.
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PMID:Peptides as putative excitatory neurotransmitters: carnosine, enkephalin, substance P and TRH. 615 51

The application of Coon's indirect method, using antisubstance P antibodies, has permitted the immuno-histo-fluorescence study of the distribution of SP positive structures in 6 human brains. Several areas of the hemispheres and of the brainstem have shown axons of various sizes and densities exhibiting SP positive varicosities. Their topographic distribution was established for the human brain and compared with the distribution observed in the brain of the rat. Both distributions appeared very similar in the somato-sensorial systems of the spinal cord, medulla and pons, in the structures of the midbrain tectum and tegmentum as well as in those of the thalamus and hypothalamus. Substantia nigra and globus pallidus showed a large amount of substance P, in human brain as well as in the rat, but in human brain, substance P positive axons were arranged in a longitudinal peridendritic "pipe" shaped manner, particularly in the antero-external and superior part of the substantia nigra as well as in the internal segment of the globus pallidus; such "pipes" were rarely seen in the rat. Moreover, in man, the pallidal substance P was almost exclusively seen in the internal segment while it spreads to the external segment in the rat. Substance P was found to be scarce in the rhinencephalic and limbic structures, the amygdala and the olfactory bulb of man, contrary to their abundance in the rat, but this peculiarity could be due more to some pathological changes associated with the advanced age of the patients whose brains were studied than to an interspecific difference.
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PMID:[The morphology of substance P in the human brain as determined by an immuno-histo-fluorescence study]. 616 43

With the indirect immunofluorescence technique of Coons, the overall distribution of the substance P (SP)-positive neuron system in the frog brain and spinal cord was explored. SP-positive cells were observed in more than ten areas, such as olfactory bulb, amygdaloid complex, septal area, bed nucleus of hippocampal commissure, hypothalamic periventricular zone, dorsal and ventral thalamus, infundibulum, torus semicircularis, optic tectum, the area dorsal to the interpeduncular nucleus, central gray matter of the mesorhombencephalon, and raphe region, etc. A dense network of SP-positive fibers was also widely distributed in the frog brain and spinal cord. SP-positive fibers were roughly divided into two types. One consisted of very fine SP-positive fibers and gave the region a diffuse appearance. The area medial to n. Bellonci, interpeduncular nucleus, n. isthmi, and optic tectum contained this type of SP-positive fibers. The other one consisted of clearly distinguishable varicose fibers. A number of SP-positive fibers located in the amygdaloid complex, striatal complex, hypothalamus, central gray matter of the mesorhombencephalon, trigeminal spinal nucleus, and posterior horn of the spinal cord belonged to this category. The functional role of the SP-positive neuron system in the central nervous system is also briefly discussed.
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PMID:Regional distribution of substance P-like immunoreactivity in the frog brain and spinal cord: immunohistochemical analysis. 616 47

Methionine-enkephalin, substance P, and somatostatin immunoreactivities are associated with different classes of neurons in the main olfactory bulb of the hamster. In the glomerular layer, methionine-enkephalin immunoreactivity is observed in the somata and dendrites of periglomerular cells whereas substance P immunoreactivity is present in the somata and dendrites of external tufted cells. Substance P immunoreactivity may also be present in the superficial short axon cells. In the deeper layers, methionine-enkephalin immunoreactivity is observed in a mixed population of neurons which appear to be primarily granule cells, whereas somatostatin immunoreactivity is present only in deep short axon cells. Methionine-enkephalin-, substance P-, and somatostatin-positive fibers of central origin are also observed in the main olfactory bulb.
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PMID:Localization of methionine-enkephalin, substance P, and somatostatin immunoreactivities in the main olfactory bulb of the hamster. 617 55


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