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)

Nedocromil sodium is a new chemical entity. This compound is very hydrophilic and is well absorbed by tissues such as the lung but not by tissues with tight junctions such as the gut. This product is chemically different from all drugs currently used for the treatment of airway diseases. The in vitro effects of nedocromil sodium are reviewed. Nedocromil sodium is capable of blocking: 1) the chemotaxis of neutrophils; 2) the activation of macrophages and monocytes by IgE; 3) the release of histamine from mast cells; 4) the cytotoxicity of platelets; 5) the release of LTC4 from eosinophils. Nedocromil sodium thus seems to have an effect on each of the cells which are implicated in the allergic reactions. In animals, nedocromil sodium can block the immediate bronchoconstriction induced by an antigen, adenosine and neurokinin A. Nedocromil sodium can also block the increase in bronchial responsiveness induced by antigen exposure. Moreover, vascular permeability induced by ovalbumin is reduced by nedocromil sodium. In summary, nedocromil sodium demonstrated a significant inhibitory effect of inflammation in both in vivo and in vitro models.
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PMID:[Basic research on nedocromil sodium]. 131 52

Several neurotransmitters have been reported to exist in the ganglionated plexus of the guinea pig gallbladder. These include substance P, neuropeptide Y (NPY), calcitonin gene-related peptide, vasoactive intestinal peptide (VIP), acetylcholine, norepinephrine, serotonin, and dopamine. To determine which neuropeptides are intrinsic to gallbladder ganglia, we performed immunohistochemistry on colchicine-treated preparations. In separate, single-labeled preparations, a majority of neurons contained substance P-, NPY-, or somatostatin-like immunoreactivity. In double-labeled preparations, a large majority of the neurons that contained substance P-like immunoreactivity also contained NPY-like immunoreactivity and somatostatin-like immunoreactivity. Immunoreactivity for VIP was present in a small percentage of the gallbladder neurons which did not contain substance P-like immunoreactivity. Additional experiments were done to test for the presence of other compounds, known to exist in the neurons of the gut. Although immunoreactivity was found in control preparations of small intestine, the ganglionated plexus of the gallbladder lacked immunoreactivity for galanin, dynorphin, enkephalin, gastrin-releasing peptide, or gamma-aminobutyric acid. We conclude that ganglia of the guinea pig gallbladder contain at least two populations of neurons, based on transmitter phenotype. One of these populations appears to contain substance P, NPY, and somatostatin. Another population, which represents a small contingent of the total population of neurons, contains VIP.
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PMID:Transmitter diversity in ganglion cells of the guinea pig gallbladder: an immunohistochemical study. 134 12

This study was designed to test the hypothesis that stimulation of adenylate cyclase and elevation of cAMP is involved in the signal transduction process for substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, cholecystokinin or gastrin releasing peptide in myenteric ganglia. Enzymatically dissociated ganglia from the myenteric plexus of the guinea-pig small intestine were used to study changes in levels of cAMP in response to application of the brain-gut peptides in the presence and absence of forskolin. Application of substance P and calcitonin gene-related peptide were found to increase intraganglionic cAMP in a dose-dependent fashion when a phosphodiesterase inhibitor was present. The ED50 values for substance P and calcitonin gene-related peptide were 5 microM and 0.75 microM, respectively. The presence of forskolin in the incubation medium resulted in significant upward shifts of the dose-response curves for both peptides. Neither vasoactive intestinal peptide, cholecystokinin nor gastrin releasing peptide stimulated increases in intraganglionic cAMP under the same experimental conditions used for substance P and calcitonin gene-related peptide.
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PMID:Effects of brain-gut related peptides on cAMP levels in myenteric ganglia of guinea-pig small intestine. 137 54

The peptide substance P has been recognized for years as having dramatic effects on such diverse physiological responses as blood pressure regulation, peristalsis of the gut, and salivation. More recently, demonstration of substance P receptors on leukocytes and modulation of leukocyte functions by this peptide suggested that it might also have a role in immune regulation. This review focuses on the growing body of evidence that demonstrates substance P-induced effects on one population of leukocytes, namely B lymphocytes. Despite the diversity of experimental techniques used, there is surprisingly good agreement as to the role substance P has in modulating B lymphocyte responses. In vivo treatments of rodents, which increase substance P concentrations in the periphery, increase the number of immunoglobulin-secreting cells in these animals. Conversely, infusion of substance P antagonists or depletion of substance P-containing neurons in rodents substantially reduces the animals' ability to synthesize immunoglobulins. With the use of cultures of B lymphocytes it was possible to demonstrate similar results. In the presence of polyclonal B cell activators, substance P augmented immunoglobulin secretion in cultures of purified B lymphocytes or B cell clones. The absence of accessory cells in these cultures suggested that substance P could act directly on activated B lymphocytes, and in fact these B cells were shown to express specific receptors for this peptide. It appears that the substance P receptors expressed by leukocytes are similar or identical to those expressed by neurons as evidenced by radioreceptor binding assays and detection of the gene encoding the substance P receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Substance P: a late-acting B lymphocyte differentiation cofactor. 137 76

Substance P (SP), a neuropeptide found in high concentrations in the gut, is reported to have many potent immunomodulatory actions. This study evaluated some effects of SP on human peripheral blood lymphocytes (PBL) and jejunal intraepithelial lymphocytes (IEL) and the expression of SP receptors on these and other lymphocytes types. In contrast to previous studies, SP (10(-8) or 10(-12) M) did not affect the proliferation (spontaneous or mitogen-induced) nor spontaneous cytotoxicity by PBL or IEL. To determine whether this unresponsiveness was due to an absence of SP receptors, the SP binding potential of these and other human lymphocyte types was determined by Scatchard analysis of radioligand binding. The IM-9 B lymphoblastoid cell line, used as a positive control, demonstrated 4838 +/- 603 or 3131 +/- 832 receptors per cell, with a Kd of 0.21 +/- 0.01 or 0.18 +/- 0.09 nM, using [3H]SP or 125I-SP, respectively. No receptors were found on PBL, polymorphonuclear leukocytes, splenocytes, IEL, or jejunal lamina propria lymphocytes using either radioligand. These findings dispute the presence of large numbers of SP receptors on lymphocytes in peripheral blood, spleen, or intestinal mucosa, and argue against any major effect of SP on T cell proliferation or spontaneous cytotoxicity.
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PMID:Human lymphocytes lack substance P receptors. 137 92

1. The effect of newly developed, receptor-selective tachykinin antagonists (GR 71,251 for NK1 receptors, MEN 10,376 and L 659,877 for NK2 receptors) on noncholinergic transmission to the circular muscle of the guinea-pig ileum has been investigated. 2. In circular muscle strips of the ileum, electrical field stimulation in the presence of atropine (2 microM) and apamin (0.1 microM) evoked a complex motor response. The tonic primary contraction in this response was reduced by GR 71,251 (10 microM) and MEN 10,376 (3-10 microM) but not by L 659,877 (up to 10 microM). The presence of apamin was necessary in this experimental arrangement to unmask an atropine-resistant primary contraction, sensitive to tachykinin antagonists. The motor response was abolished by tetrodotoxin. 3. In circular strips of the ileum GR 71,251 (10 microM) inhibited the tonic contraction produced by [Sar9] substance P sulphone, a selective NK1 receptor agonist but not that produced by [beta Ala8] neurokinin A (4-10), a selective NK2 receptor agonist. By contrast, MEN 10,376 antagonized the effect of the NK2 agonist while leaving the response to the NK1 agonist unaffected. 4. In whole segments of the ileum, distension of the gut wall by an intraluminal balloon placed at about 1 cm from the point of recording of mechanical activity of the circular muscle produced atropine-sensitive phasic contractions (ascending enteric reflex). In the presence of atropine (2 microM), a noncholinergic response was elicited, which required larger volumes of distension that the cholinergic one. The atropine-resistant ascending enteric reflex was enhanced by apamin (0.1 microM) and abolished by tetrodotoxin, either in the presence or absence of apamin.5. MEN 10,376 (3-lOmicroM) inhibited the atropine-resistant ascending enteric reflex in the presence of apamin while GR 71,251 or L 659,877 (10 microM each) were ineffective. MEN 10,376 inhibited the atropine-resistant ascending enteric reflex to a larger extent in the absence than in the presence of apamin and also slightly inhibited the ascending enteric reflex in the absence of atropine.6. These findings provide evidence for an involvement of NK2 tachykinin receptors in excitatory transmission to the circular muscle of the guinea-pig ileum. NK2 receptors are also involved in the physiological-like circular muscle activation produced by stimulation of intramural neuronal pathways which subserve the atropine-resistant ascending enteric reflex.
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PMID:Tachykininergic transmission to the circular muscle of the guinea-pig ileum: evidence for the involvement of NK2 receptors. 138 Mar 73

Certain brain gut-peptides are known to either stimulate or inhibit gastric acid secretion in several species after direct injection into the central nervous system. However there is inconsistency of published results on the gastric acid secretory response to some of these peptides after peripheral administration in different experimental systems. Seven peptides, namely neurotensin (NT), substance P, cholecystokinin (CCK), thyrotropin releasing hormone (TRH), human calcitonin (hCT), rat calcitonin-gene-related peptide (rCGRP) and bombesin, all known to modulate gastric acid secretion after central administration, were initially screened for activity after peripheral (subcutaneous) injection of 10 micrograms/kg body weight in a single rat model. Peptides showing an effect were retested at lower doses. Despite the inherent variability of the gastric acid secretory response in the non-anaesthetized pylorus ligated rat, a standardized experimental design confirmed that reproducible and statistically valid results could be obtained. The technical feasibility of using a one hour collection period as might be appropriate for short acting peptides was demonstrated by the significant dose dependent inhibitory activity of salmon calcitonin. In this model, NT and substance P had no significant effect on either volume or concentration of acid secreted, CCK showed a slight stimulation of acid output, and TRH, hCT, rCGRP and bombesin all inhibited acid output; CGRP and bombesin were active at 10 and 100-fold lower doses. The potent and inhibitory activity of bombesin in this system is in disagreement with other publications reporting no effect or variable stimulatory effect in rats. Time and dose dependent responses in our rat system indicate that this apparent discrepancy may be explained by the short duration of action of bombesin.
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PMID:The short term effect of peripherally administered brain-gut peptides on gastric acid secretion in rats. 138 Jul 63

The present work was undertaken to determine by immunocytochemical methods which of the putative enteric neurotransmitters are contained in axons supplying the guinea-pig taenia coli and what proportion of axons is accounted for by the presence of these substances. Numerous fibres displayed immunoreactivity for dynorphin (DYN), enkephalin (ENK), gamma-aminobutyric acid (GABA), nitric oxide synthase (NOS), substance P (SP) and vasoactive intestinal peptide (VIP), but, in contrast to other gut regions, fibres showing immunoreactivity for gastrin-releasing peptide, galanin and neuropeptide Y were rare in the taenia. Fibres reactive for calbindin, calcitonin gene-related peptide, cholecystokinin, 5-hydroxytryptamine and somatostatin were also rare. Tyrosine hydroxylase-like immunoreactivity (TH-LI) was present in numerous fibres that disappeared after extrinsic denervation, a procedure that did not detectably affect any of the other major groups of fibres. Simultaneous staining of extrinsically denervated preparations revealed that SP-LI and VIP-LI were located in separate fibres, and ultrastructural studies showed these to be 58% and 33% of intrinsic fibres supplying the muscle. Immunoreactivity for the general marker, neuron-specific enolase, was located in 95-98% of axons. ENK-LI and DYN-LI were in the same axons, and similar proportions of the fibres with either SP-LI or VIP-LI, about 85%, contained immunoreactivity for ENK and DYN. All VIP-LI fibres, but no SP-LI fibres, were reactive for NOS. The results imply that the taenia of the guinea-pig caecum is innervated by two major groups of enteric neurons: (i) excitatory neurons that contain ACh, SP, other tachykinins, and, in most cases, DYN-LI and ENK-LI; and (ii) inhibitory neurons that contain NOS-LI, VIP-LI, in most cases, the two opioids and, quite probably, ATP as a transmitter. GABA-LI is contained in a smaller population of intrinsic axons. Even though the taenia represents one of the simplest tissues for examining transmission from enteric neurons to intestinal muscle, it shares some of the complexity of other regions, in that four major axon types supply the muscle and both the enteric excitatory and enteric inhibitory neurons contain multiple transmitters.
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PMID:Light- and electron-microscopic immunochemical analysis of nerve fibre types innervating the taenia of the guinea-pig caecum. 138 81

Immunocytochemical expression of the low-affinity nerve growth factor receptor was studied in human fetal and adult tissues using the monoclonal antibody ME20.4. In dorsal root ganglia, a few immunoreactive neurons were first detected in nine-week-old fetuses and many more were found in the following weeks of gestation. However, none was present in adult ganglia. The ME20.4-positive cells were larger than neurons immunostained by substance P, calcitonin gene-related peptide or galanin antibodies. In the spinal cord, fibres immunostained by ME20.4 appeared in a characteristic pattern that differed from the spatial and temporal distributions of synaptophysin- and neurofilament-immunoreactive fibres. Those expressing the low-affinity nerve growth factor receptor were only detected in regions containing collaterals of primary sensory axons: (i) in the dorsal funiculus between seven and 18 weeks of gestation; (ii) in a ventrodorsal bundle reaching the ventral horn from weeks 12-14; (iii) in the medial region of the dorsal horn between weeks 12 and 20; (iv) in the superficial layers and lateral portion of the dorsal horn after the 14th week of gestation and also in adult spinal cord. During the fetal period, ME20.4 immunoreactivity was also found in motoneurons and peripheral nerve fibres in the skin, myotomes and gut. Sheaths of peripheral nerves and the adventitia of blood vessels were stained both in fetal and adult tissues. Thus, the low-affinity nerve growth factor receptor is: (i) strongly expressed in the developing human nervous system; (ii) transiently associated with a subset of large primary sensory neurons and with motoneurons; (iii) transiently and sequentially expressed by various groups of sensory afferents to the spinal cord; (iv) permanently expressed by fibres in the superficial layers of the dorsal horn, Clarke's column, nerve sheaths and the adventitia of blood vessels.
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PMID:Developmental pattern and distribution of nerve growth factor low-affinity receptor immunoreactivity in human spinal cord and dorsal root ganglia: comparison with synaptophysin, neurofilament and neuropeptide immunoreactivities. 143 99

The pattern of nerve cells and fibers containing calcitonin gene-related peptide immunoreactivity (CGRP-IR) was investigated in the canine digestive tract by means of immunohistochemistry. CGRP-IR nerve fibers innervate all the layers of the gut, including the vasculature, with different densities depending on the region. CGRP-IR processes are sparse in the esophagus and stomach, where they are mostly confined to the enteric plexuses and vasculature. CGRP-IR fibers are quite abundant in the small and large intestine, where they form dense arborizations in the mucosa, and are numerous in the muscularis mucosae, deep muscular plexus and circular muscle. The myenteric and submucous plexuses of the intestine contain dense networks of CGRP-IR fibers and numerous CGRP-IR ganglion cells. On the other hand, in the enteric ganglia of the esophagus and stomach, in the intrapancreatic ganglia and in the ganglionated plexus of the gallbladder, CGRP-IR is restricted to non-varicose processes. A moderate density of CGRP-IR fibers supplies the endocrine and exocrine pancreas, and the fibromuscular layer and lamina propria of the gallbladder. The density of CGRP innervation in different regions can be summarized as follows: intestine >> pancreas and gallbladder > or = antrum > cardia > gastric corpus and distal esophagus. CGRP- and tachykinin (TK)-IRs are colocalized in a substantial population of fibers, particularly those distributed to the mucosa, muscularis mucosae and vasculature, whereas there was no evidence of colocalization in intrinsic ganglion cells. The present results suggest that (1) the CGRP innervation of the dog digestive system includes an intrinsic and an extrinsic component, and (2) CGRP- and TK-IRs are co-expressed in extrinsic nerve fibers. These findings extend previous observations in rats and guinea pigs and provide insights into the sites of action of CGRP in the digestive system of the dog, which has served as a model for CGRP functional studies.
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PMID:Calcitonin gene-related peptide neurons innervating the canine digestive system. 147 4


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