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)

A general model of the autonomic neuroeffector junction is proposed. In this model, emphasis is placed on the muscle effector bundle with electrotonic coupling between individual cells via gap junctions (or nexuses) and en passage release of transmitter from autonomic nerve varicosities. This release results in transmission to effector cells across junctional clefts ranging from about 20 nm in the vas deferens and iris to as much as 2000 nm in some large arteries. The ultrastructural identification of different autonomic nerve types is described. Current theories on the synthesis, storage, release, and inactivation of transmitter during cholinergic, adrenergic, and purinergic transmission are summarized. Some speculations are made about the possible involvement of purinergic nerves in the innervation of vessels and mast cells in the skin, and whether this involvement results in a functional link between ATP, histamine, bradykinin, and prostaglandin in cutaneous vasodilatation. Another possibility considered as the basis for this reflex is the release of substance P from sensory (pain) nerve collaterals in the skin.
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PMID:Autonomic neuroeffector junctions--reflex vasodilatation of the skin. 1 40

1. A morphological and physiological comparison was made between embryonically and postnatally derived superior cervical ganglion neurons (SCGN) grown in dissociated cell culture. It was found that while morphologically distinct, the physiological properties of the postnatal neurons were the same as their embryonic counterparts. 2. Intracellular injection of horseradish peroxidase (HPR) demonstrated that SCGN from any age of animal elaborated two basic types of processes, although the pattern of process ramification was unique for each neuron. The two types of proceses were 1) the large, smooth, rapidly tapering; and 2) the thin, nontapering variety, which often contained varicosities along its length. It is suggested that the former are dendritic in function, while the latter act as axons. 3. A difference was noted in somal size and the number of primary processes extended by the embryonic and postnatal neurons, with the latter more closely resembling the in vivo morphology. 4. Resting potentials and action-potential amplitudes of postnatal SCGN were comparable to those found previously for embryonic SCGN in vitro. 5. Iontophoretic application of putative neurotransmitter substances revealed the presence of acetylcholine receptors (AChR) on both embryonic and postnatal SCGN. Picrotoxin-sensitive depolarizing responses to iontophoresed gamma-aminobutyric acid (GABA) was seen on a few embryonic neurons, but not on the older cells. No responses were detected when norepinephrine (NE), glutamate, cAMP, substance P, or dopamine were applied to the SCGN of either age group. 6. Synatpic interaction between postnatal SCGN were found at an earlier in vitro age (12 days) than was the case for embryonic neurons (20 days). 7. Synaptic transmission was found to be chemical in nature. This was shown by 1) a dependence on external Ca2+ concentrations; 2) steplike fluctuations in synpatic potential amplitude, and 3) a variation in potential amplitude with changes in membrane potential. 8. It is concluded that the postnatal SCGN are able to survive in culture even when taken from animals up to 12.5 wk old. The elaboration of processes is in many ways strikingly similar to sympathetic neurons in the animal, and they are able to form functional synaptic interactions.
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PMID:Postnatal rat sympathetic neurons in culture. I. A comparison with embryonic neurons. 3 83

The unlabeled substance P (SP) antibody-peroxidase-antiperoxidase reaction was used on tissue prior to embedding in epoxy reins for ultrastructural identification of the SP cell and its immunoreactive granules. The SP cell is 10-20 mum in diameter and has sparse cytoplasm with numerous intensely reactive SP granules 100-300 nm across, large clear vacuoles, elaborate smooth endoplasmic reticulum, fragmentary rough endoplasmic reticulum, dispersed ribosomes, few mitochondria, and a modest Glogi apparatus. The large SP-reactive granules are discharged into the extracellular space, either with cell membrane intact or as unbound dense material. The membrane-bound dense granucles are transported intact through endothelial cells into the blood or are picked up by Schwann cells and fibroblasts. Other SP-reactive granules lose their limiting membranes, fragment, and then disperse into fine immunoreactive grains that bind to the extracellular matrix and to collagen. Dispersed SP-reactive granules are transported within myriad pinocytotic vesicles across endothelial cells with numerous luminal plications and are discharged into the blood. Pinocytosis of dispersed SP-reactive material, that can be detected intracellularly, also occurs in Schwann cells and fibroblasts. The SP axons to the substantia gleatinosa are unmyelinated or finely myelinated. Their synaptic varicosities display a generalized axoplasmic immunoreactivity, which also occurs in and around small vesicles. The larger SP synaptic vesicles are intensely reactive.
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PMID:Ultrastructural identification of substance P cells and their processes in rat sensory ganglia and their terminals in the spinal cord by immunocytochemistry. 33 57

Immunocytochemical techniques locating neurotransmitter-synthsizing enzymes are currently being employed to determine the nature of transmitters associated with individual neurons. The use of peroxidase-anti-peroxidase Fab (PAP Fab) complex modified from Sternberger's PAP method, among several other immunocytochemical methods is recommended for the visualization of antigens in cerebral tissues. The enzyme fixed in nervous tissues is reacted with anti-enzyme produced in rabbits followed by incubation with goat-anti-rabbit serum. Subsequent application of PAP Fab complex prepared separately results in a formation of a complex composed of enzyme: anti-enzyme: goat-anti-rabbits: PAP-Fab. The enzymes can be visualized under light and electron microscope by the deposition produced by the action of peroxidase on 3,3'-diaminobenzidine. Thus, the antibody to glutamate decarboxylase (GAD), the enzyme that synthesizes gamma-aminobutyric acid (GABA) was employed to identify GABAergic neurons in central nervous system of rodents. Specific staining for GAD was highly localized in close association with synaptic vesicles in certain axon terminals including basket, Golgi and the Purkinje cell terminals in the cerebellum. The distribution of GAD observed in immunocytochemical preparations was consistent with indirect biochemical, physiological and morphological data dealing with the synaptic role of GABA neurons in the cerebellum. The correlation of the immunocytochemical distribution of GABA neurons in the spinal cord, substantia nigra, olfactory bulb, retina and Ammon's horn with physiological and biochemical results can also been obtained. The method has been successfully employed to visualize dopamine-beta-hydroxylase (DBH) and substance P. DBH, as an indicative enzyme for noradrenergic (NA) neurons, was highly localized in the neuronal soma of the locus coeruleus and in synaptic varicosities in the stria terminalis associated with synaptic vesicles. Association of substance P in probable primary afferent terminals with large vesicles also supports the synaptic function of the compound in the spinal cord.
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PMID:[Immunocytochemical technique--Application for identifying GABA neurons (author's transl)]. 35 33

Developmental changes in the coexistence of serotonin and substance P/enkephalin within single fibers of lamina IX of the rat lumbar spinal cord were examined by the use of a double-labelling immunohistochemical technique. On postnatal day (P) 0, 65.0% of immunoreactive varicosities contained only serotonin, and 21.3% of them had both serotonin and substance P. The coexistent ratio of serotonin and substance P in single fibers increased with development: 61.9% of serotonin positive varicosities co-contained substance P on P28, similar to the ratio found in adult animals (67.4%). The ratios of varicosities containing only substance P remained the same from P0 to adult stage (about 15%). Enkephalin positive immunoreactivity was not co-localized with serotonin positive varicosities at any stage of development. Although numerous serotonin positive fibers were found in lamina IX, only a few substance P and enkephalin positive fibers were observed in the same area on P0. The density of serotonin positive varicosities increased slightly by P28, whereas substance P and enkephalin positive fibers increased considerably by this age. Between P28 and the adult stage, the density of serotonin positive fibers decreased by about 50%. The cross sectional area of axonal varicosities containing serotonin- and substance P-like immunoreactivity was similar in both P0 and adult animals, whereas that of enkephalin positive fibers was different. We also examined the coexistence of serotonin and substance P within single neurons of the caudal raphe nuclei in P7 and adult animals, and found that the coexistent ratio significantly increased with development.
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PMID:Immunohistochemical study on development of serotonin-, substance P-, and enkephalin-positive fibers in the rat spinal motor nucleus. 128 Feb 85

Previous studies have suggested that peptides such as substance P and thyrotropin-releasing hormone coexist with serotonin in the same varicosities in the ventral horn and intermediate gray of the spinal cord in rat. However, coexistence of these peptides with serotonin is rare in fibers in the superficial dorsal horn. Since it has been proposed that serotonergic fibers in the superficial dorsal horn act to modulate nociception, it was hypothesized that the serotonergic neurons that contain neither substance P nor thyrotropin-releasing hormone might constitute a specifically antinociceptive subset of serotonergic neurons. This being the case, it would be expected that different types of serotonergic neurons innervate nociceptive and non-nociceptive spinal neurons. In order to test this hypothesis, a group of cells that include nociceptive neurons (spinothalamic tract neurons) and a group of predominantly non-nociceptive neurons (postsynaptic dorsal column neurons) in the spinal cord of rat were retrogradely labeled. Sections of the spinal cord containing retrogradely labeled spinothalamic tract or postsynaptic dorsal column neurons were stained for serotonin and either substance P or thyrotropin-releasing hormone using two-color immunohistochemistry. A retrogradely labeled cell was classified as "apposed" if there was no discernible distance between an immunohistochemically labeled varicosity and the cell. Eighty per cent of spinothalamic tract and 83% of postsynaptic dorsal column profiles were apposed by serotonin-immunoreactive varicosities in the spinal cord. Thirty-one per cent of the spinothalamic tract profiles that were apposed by serotonergic varicosities were apposed by serotonergic varicosities that were also stained for thyrotropin-releasing hormone. The distribution of the latter spinothalamic neurons was similar to that reported for spinothalamic tract neurons responsive to joint movement. In addition, at least 63% of the spinothalamic tract profiles which were apposed by serotonergic varicosities were apposed by "serotonin-only" varicosities, including most spinothalamic tract neurons in the marginal zone, suggesting that at least some "serotonin-only" neurons are antinociceptive. However, contrary to the hypothesis, at least 94% of the postsynaptic dorsal column profiles apposed by serotonergic varicosities were apposed by "serotonin-only" varicosities. These findings suggest that there may be a relationship between the sensory modality to which a spinal neuron responds and the type of serotonergic innervation it receives. However, it appears that "serotonin-only" neurons may not constitute a specifically antinociceptive category of serotonergic neurons.
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PMID:Organization of the serotonergic innervation of spinal neurons in rats--I. Neuropeptide coexistence in varicosities innervating some spinothalamic tract neurons but not in those innervating postsynaptic dorsal column neurons. 128 Mar 50

The distribution and quantity of neuropeptides in the rat pterygopalatine ganglion were studied by using complete serial paraffin sections of the ganglion immunostained with antiserum against several neuropeptides. The pterygopalatine ganglion, composed of 4932 +/- 291 (mean +/- SD) neurons, was triangular in shape with a tapering caudal tail. The most commonly found peptide in neurons was vasoactive intestinal polypeptide (VIP) (99.0%), followed by neuropeptide Y (NPY) (54.1%) and enkephalin (10.5%). The rostro-ventromedial and caudal parts of the ganglion where intensely VIP-immunoreactive neurons predominate project to the nasal mucosa, while the rostro-dorsolateral part of the ganglion where NPY-immunoreactive neurons predominate projects to the Harderian gland. The coexistence of VIP/NPY (47.4%), VIP/NPY/enkephalin (6.6%) or VIP/enkephalin (3.9%) in the ganglionic neurons was recognized. Calcitonin gene-related peptide (CGRP)- and substance P-immunoreactive varicosities formed synaptic contacts with the somatic spine or soma, which confirmed that the reflex arch, composed of axon collaterals of trigeminal ganglionic neurons and parasympathetic ganglionic neurons, operates through direct synapses. Enkephalin-immunoreactive varicosities, which were probably derived from parasympathetic preganglionic neurons, also made synaptic contact with the somatic spine.
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PMID:Distribution of neuropeptides in rat pterygopalatine ganglion: light and electron microscopic immunohistochemical studies. 128 5

Superior cervical ganglia from 7 human cadavers (3-7 h post mortem) were immunostained for tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and 14 different neuropeptides. The results show that ganglionic cells contain TH, DBH, neuropeptide Y (NPY), somatostatin, vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP). These substances were present predominantly within large ganglionic cells. Inside the ganglion, the number and topographical distribution of various types of immunoreactive cells differed from one another. NPY and CGRP immunoreactivities were found in some TH-positive cells, but that co-localization never exceeded the 30% of the TH cells. Leu-enkephalin showed a weak immunoreactivity, which was restricted to fibers or varicosities. Neuropeptides like substance P, dynorphin A and B, cholecystokinin, galanin, corticotropin-releasing factor, thyrotropin-releasing hormone, angiotensin II and neurotensin showed no immunoreactivity in the human superior cervical ganglion.
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PMID:Neuropeptides in the human superior cervical ganglion. 135 73

A perifused preparation of guinea pig myenteric nerve varicosities (synaptosomes) was used to determine the characteristics of evoked tachykinin release and the inhibition of such release by adenosine analogues. Release of substance P-like immunoreactivity (SP-LI) and neurokinin A-like immunoreactivity (NKA-LI) was evoked by elevated extracellular [K+] in a reversible and repeatable manner. This release was completely abolished in the absence of extracellular Ca2+. Perifusion in the presence of 5'-N-ethylcarboxamidoadenosine (NECA), a nonselective A1/A2 adenosine receptor agonist, decreased K(+)-evoked release of SP-LI and NKA-LI compared with that in the absence of the nucleoside. Similar decrements in peptide release were obtained with N6-cyclopentyl adenosine (CPA), a selective A1 agonist, and 2-[p-(2-carboxyethyl)]phenethylamino-5'-N-ethyl-carboxamidoadenosi ne (CGS 21680), a selective A2 agonist. Response to all nucleosides was graded. Potency order of adenosine analogues was CPA greater than NECA much greater than CGS 21680. Inhibition due to the nucleosides was diminished in the presence of the highly selective A1-receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) while perifusion in the presence of DPCPX alone did not alter evoked release of either peptide. These findings provide direct measurements of inhibitory effects of adenine nucleosides on the release, from enteric nerve endings, of endogenous neuromediators SP and NKA. The findings also directly demonstrate the presence of functional adenosine receptors of the A1 subtype on enteric nerve endings coupled negatively to release of tachykinins. The presence of A2 receptors on enteric nerve endings is neither supported nor excluded.
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PMID:Adenosine A1 receptors mediate inhibition of tachykinin release from perifused enteric nerve endings. 137 85

Substance P is one of the peptides released from sensory nerves that mediate "neurogenic inflammation." Although substance P-immunoreactive (SP-IR) axons are known to be present within the mucosa of the respiratory tract, the relative extent of the innervation of various components of the mucosa is not known. Therefore, we determined the distribution and number of SP-IR axons in the rat trachea and bronchi, by using immunohistochemistry on tissue whole mounts. Specifically, we sought to learn whether these axons directly innervate the postcapillary venules involved in neurogenic plasma extravasation, the arterioles involved in neurogenic vasodilatation, and the airway smooth muscle involved in bronchoconstriction in pathogen-free, adult male F344 rats. We found that 90% of the SP-IR axons were single axons, usually having varicosities. Eighty-five percent of these were in the epithelium, 6% innervated arterioles, and the remainder elsewhere in the lamina propria. Only 10% of the mediator-sensitive postcapillary venules (i.e., venules labeled with Monastral blue pigment after challenge with capsaicin or substance P) were within 10 microns of SP-IR axons. SP-IR axons were more than 10 times as frequent in the smooth muscle of the distal bronchi as in the trachea. Capsaicin pretreatment (168 mg/kg over 7 days) reduced the number of SP-IR axons in the trachea by 96%, which is consistent with their being sensory. Unilateral vagotomy reduced the number of SP-IR axons bilaterally in the trachea and ipsilaterally in the main stem bronchus. Using an antibody to Protein Gene Product 9.5 as a nonspecific marker for all nerves in the trachea, we determined that SP-IR axons constituted 90% of the axons in the epithelium, 32% of the axons on arterioles, and only 4% of the axons in the smooth muscle. We conclude that most SP-IR nerves in the trachea are sensory axons and most of these axons end in the epithelium. SP-IR axons innervate mucosal arterioles, but few innervate postcapillary venules. Therefore, the mechanism by which sensory axons evoke plasma extravasation from these venules is likely to involve the diffusion of the peptide or a secondary mediator from the epithelium or from the arterioles upstream.
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PMID:Substance P-immunoreactive sensory axons in the rat respiratory tract: a quantitative study of their distribution and role in neurogenic inflammation. 137 14


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