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)

Enkephalinergic axons and terminals were identified by the PAP immunohistochemical method in lamina I (marginal zone) and lamina IIO (outer substantia gelatinosa) in the dorsal horn of the monkey spinal cord. Synaptic profiles with enkephalin-like immunoreactivity (MELI) contained clear, round, vesicles, sometimes a few large granular vesicles, and usually formed asymmetrical contacts. MELI terminals forming synaptic contacts with various sizes of dendrites and with dendritic spines were the most common type of relationship found; axosomatic contacts were few. Additionally, two types of complexes were observed in which an MELI terminal formed a specialized apposition with an unlabelled terminal. The contact often resembled a synapse and in most cases the MELI terminal was suspected to be presynaptic. One complex consisted of a MELI terminal apposing the LGV type terminal (containing large granular vesicles), which in turn was presynaptic to a dendrite. (The identity of the LGV terminal could not be determined, but it had some characteristics similar to those described for substance P terminals and for a class of primary afferents in the monkey dorsal horn). The other type of complex consisted of a MELI terminal apposing an R-type terminal (containing small, round, clear vesicles) which was in turn presynaptic to a dendrite. Often, the MELI terminal also formed a synapse onto the same dendrite. The axodendritic, axospinous and axosomatic contacts of MELI terminals in the superficial dorsal horn may produce some of the depressive postsynaptic-like effects of enkephalin iontophoresis onto dorsal horn neurons. In these cases the responses of dorsal horn neurons to both low threshold and nociceptive primary afferents is suppressed. However, the opiate receptor-dependent PAD of C-fibers observed in the dorsal horn may be mediated by the MELI complexes formed with LGV and R terminals found in lamina I.
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PMID:Ultrastructure of chemically defined neuron systems in the dorsal horn of the monkey. II. Methionine-enkephalin immunoreactivity. 635 63

The ultrastructural organization of serotoninergic axons and terminals in the superficial dorsal horn of the monkey was examined by the PAP immunohistochemical method. Terminals with serotonin-like immunoreactivity (SLI) were identified in lamina I (marginal zone) and lamina IIo (outer substantia gelatinosa). Labelled profiles contained many small, round, clear vesicles and usually a few granular vesicles (70 nm diameter). Most synaptic junctions were symmetrical with sparse pre- and post-synaptic densities. Most frequently, terminals formed axodendritic synapses on large and small dendrites; axosomatic and axospinous contacts were infrequent. In addition SLI terminals were found apposed to unlabelled LGV-type terminals (containing several large granular vesicles of 75-90 nm). The appositions commonly met some criteria of axo-axonic synapses and the SLI terminal was suspected to be presynaptic. The unlabelled LGV terminal was often presynaptic to a dendrite, and it had characteristics similar to those observed for some primary afferents, particularly those which may contain substance P, a proposed transmitter for nociceptive C-fibers. Most of these 'triplet' complexes (SLI terminal apposing and LGV terminal synapsing onto dendrite) were found in the apical region of lamina I. The axodendritic and axosomatic serotoninergic contacts onto dorsal horn neurons may be a basis for some of the reported post-synaptic effects on dorsal horn cells of either local serotonin iontophoresis or of stimulation of the brainstem raphe, the probable origin of the serotoninergic terminals. These effects include both depression and excitation of the responses of the dorsal horn cells to electrical or natural stimulation of primary afferents, particularly C-fibers and nociceptors. Likewise, the contacts of SLI terminals with LGV terminals may provide a morphological substrate for the presynaptic effects also observed for serotonin iontophoresis or raphe stimulation, including changes in the excitability of primary afferent C-fibers.
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PMID:Ultrastructure of chemically defined neuron systems in the dorsal horn of the monkey. III. Serotonin immunoreactivity. 661 58

Previous descriptions of immunoreactive vasoactive intestinal polypeptide (VIP) in small-diameter dorsal root ganglion cells in the superficial dorsal horn implicated this 28 amino acid peptide in nociceptive transmission. In this study, we examined the distribution of immunoreactive VIP in the spinal cord and caudal medulla of cats and rats. The PAP method was used on paraffin and frozen sections of 4% paraformaldehyde-fixed tissue, using antibodies to VIP that were raised in rabbits. The distribution of immunoreactive VIP, while similar to that of substance P (SP), a putative primary afferent peptide neurotransmitter, is more restricted. VIP staining is found in sacral dorsal roots and densely in the Lissauer tract. Dorsal horn staining is concentrated in lamina I. In contrast to SP, lamina II is almost devoid of staining. Labeled VIP axons course along the lateral curvature of the dorsal horn and arborize across lamina V and around the central canal. A collateral branch of these fibers distributes to the sacral autonomic nucleus. A few fibers could be traced from the root entry zone to the contralateral central gray. VIP axons also terminate between ependymal cells of the central canal. Unlike SP, immunoreactive VIP was restricted, almost exclusively, to the sacral cord. The few fibers in the lumbar enlargement and in the coccygeal cord apparently derive from ascending and descending sacral primary afferents. In fact, the VIP pattern is almost identical to that reported for afferents from the pelvic viscera, including a discontinuous rostrocaudal distribution. Since the staining pattern is also very similar to that of A-delta high-threshold mechanoreceptors, the possibility is discussed that whereas VIP is not a general "somatic" primary afferent transmitter, it may transmit nociceptive input from the pelvic viscera.
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PMID:Immunoreactive vasoactive intestinal polypeptide is concentrated in the sacral spinal cord: a possible marker for pelvic visceral afferent fibers. 667 14

When viewed under dark-field illumination, peptidergic terminals in sections stained by the Sternberger PAP immunocytochemical method are seen as individual points of light. Under high magnification, the degree of brightness of various areas of immunoreactive terminals is seen to be a function of the density of terminals in these areas. By analyzying the relative brightness of the immunostained central nucleus of the amygdala (CNA) with an EyeCom II PDP-11/34 image analysis system, we have obtained a relative evaluation of the density distribution of neurotensin (NT)-, substance P (SP), VIP-, angiotensin II (AII), m-enkephalin (m-ENK) and somatostatin (SS)-immunoreactive terminals in terms of normal morphology and following a brain lesion. The EyeCom II system divides the presented image into 307200 picture elements (pixels) and assigns one of 256 grey values to the average brightness with each pixel. We have aggregated the grey level frequencies into 5 levels where level 1 corresponds to the highest terminal density and level 5 to the lowest density. At level 1, only NT- and VIP-immunoreactive terminals occupy a significant percentage of the cross-sectional area of the CNA (20%). About 15% of the area of the CNA has VIP terminals with level 5 density. The distributions of the top 20% of the terminal density range of NT, SP, AII and VIP support a classical medial/lateral division of the nucleus. The distribution of the same range of SS- and ENK terminals suggests a dorsoventral division of the CNA. A preliminary study indicates that comparison of grey level frequency histograms generated by image analysis from homologous lesioned and unlesioned sections of the CNA can yield useful information regarding post-lesion changes in the distribution of immunoreactive terminals.
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PMID:Computer-assisted image analysis of the distributions of peptidergic terminals in the central nucleus of the amygdala: a preliminary study. 712 69

The synaptic relationships between primary afferent central endings containing substance P (SP) and calcitonin gene-related peptide (CGRP) and GABAergic interneurons in the guinea pig substantia gelatinosa of the lumbar spinal dorsal horn were studied. The pre-embedding PAP method was used for detection of GABA and the post-embedding double immunogold labeling method for SP and CGRP detection. Immunogold particles specific for SP and CGRP were mainly localized separately or together in large synaptic vesicles devoid of dense cores. SP and CGRP immunoreactivity was separate or co-localized in small roundish, slender, sinuous or large scalloped (fan-like) terminals with closely packed round agranular synaptic vesicles of various sizes and few large dense core vesicles and mitochondria, which are thought to be capsaicin-sensitive primary afferent terminals. These SP- and CGRP-immunoreactive boutons make presynaptic or symmetric contacts with GABAergic dendrites and soma. These findings suggest that the central endings of nociceptive primary afferents transmit pain stimuli to intrinsic inhibitory interneurons, thereby modulating nociceptive information via a postsynaptic circuit.
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PMID:Relationship of substance P- and CGRP-immunoreactive central endings of the primary afferent neurons to GABAergic interneurons in the guinea pig substantia gelatinosa. 958 14

We have previously described a novel cancer chemotherapeutic approach based on the induction of apoptosis in targeted cells by homing pro-apoptotic peptides. In order to improve this approach we developed a computational method (approach for detecting potential apoptotic peptides, APAP) to detect short PAPs, based on the prediction of the helical content of peptides, the hydrophobic moment, and the isoelectric point. PAPs are toxic against bacteria and mitochondria, but not against mammalian cells when applied extracellularly. Among other peptides, substance P was identified as a PAP and subsequently demonstrated to be a pro-apoptotic peptide experimentally. APAP thus provides a method to detect and ultimately improve pro-apoptotic peptides for chemotherapy.
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PMID:APAP, a sequence-pattern recognition approach identifies substance P as a potential apoptotic peptide. 1131 Dec 43

It is not known as to whether the Achilles and patellar tendons contain neurokinin-1 (NK-1) receptors. This is a drawback when considering the fact that pain symptoms are frequent in these and as recent studies show that the pain symptoms might be cured via interference with blood vessel function. In the present study, the human Achilles and patellar tendons were examined concerning immunohistochemical expression of the NK-1 receptor. Chemically unfixed and fixed specimens, TRITC and PAP stainings and a battery of NK-1 receptor antibodies, including antibodies against the C-terminus and the N-terminal region, were utilized. NK-1 receptor immunoreaction could be detected in inner parts of the walls of large blood vessels and in the walls of small blood vessels. To some extent, NK-1 immunoreaction was also detectable in small nerve fascicles and in tenocytes. It was found to be of utmost importance to apply both chemically unfixed and fixed specimens. The use of chemically unfixed tissue was found advantageous in order to depict the immunoreactions in the blood vessel walls. The observations represent new findings and are of relevance as substance P (SP) is known to be of importance where neurogenic angiogenesis contributes to diseases and as SP on the whole has profound effects concerning blood vessel regulation.
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PMID:Vascular NK-1 receptor occurrence in normal and chronic painful Achilles and patellar tendons: studies on chemically unfixed as well as fixed specimens. 1566 64


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