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)

Enteroendocrine cells represent the most heterogeneous population of terminally differentiated cells in the mouse intestinal epithelium. Each of the approximately 15 different enteroendocrine cell subpopulations shows characteristic distributions along both the cephalocaudal and crypt-to-villus (in the small intestine) or crypt-to-surface epithelial cuff (in the colon) axes of the gut. These cells provide a sensitive model for studying how the continuously renewing gut epithelium is able to establish and maintain its spatial differentiation. Enteroendocrine cells are derived from the same multipotent stem cell that gives rise to enterocytes and goblet and Paneth cells. Regional differences in enteroendocrine cell number and type reflect positional differences in the differentiation programs of this lineage. To better understand the nature of these programs, we used multilabel immunocytochemical methods to examine the accumulation of endogenous neuroendocrine products as well as the product of a liver fatty acid binding protein/human growth hormone transgene in enteroendocrine cells located in proximal colonic glands. The results suggest that serotonin, substance P-, glucagon-like peptide-1 (GLP-1)-, peptide tyrosine tyrosine (PYY)-, neurotensin-, and cholecystokinin (CCK)-producing cells can all arise from a single stem cell located within a given gland. Based on pairwise comparison of the coexpression of each of these six products in individual cells as well as their ability to support transgene expression, it appears that the enteroendocrine lineage has two branches; one branch produces substance P and serotonin cells while the other yields GLP-1, PYY, neurotensin, and CCK cells.
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PMID:Immunocytochemical studies suggest two pathways for enteroendocrine cell differentiation in the colon. 151 28

1. Neurokinin A (NKA) is a mammalian tachykinin distributed principally in the nervous system, including the myenteric innervation of the gut. 2. NKA may be involved in neurogenic inflammation and as a modulatory factor in the diarrhoea associated with mucosal inflammation of inflammatory bowel disease (ulcerative colitis). 3. We evaluated the effect of NKA on the short-circuit current ISC, assumed to reflect electrogenic chloride secretion, across muscle-stripped rat colonic mucosa mounted in Ussing chambers. 4. Serosal addition of NKA produced a concentration-dependent (0.1-100 nM) increase in ISC with an EC50 (half-maximal effective concentration) value of 7.5 nM. The maximum (mean +/- S.E.M.) increase in ISC (microA/cm2) for NKA was 111 +/- 10. 5. Tetrodotoxin (0.5 microM) and bumetanide (10 microM), but not atropine (1.0 microM), hexamethonium (100 microM) or pyrilamine (10 microM), significantly inhibited NKA-induced increases in ISC. 6. The response to NKA was attenuated by 45 min pre-treatment with antisera raised against vasoactive intestinal polypeptide (VIP). Moreover, prior desensitization to VIP attenuated the effect of NKA. 7. These studies suggest that NKA increases ISC in rat colon, in part, through a non-cholinergic neural mechanism involving VIP.
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PMID:Neurokinin A increases short-circuit current across rat colonic mucosa: a role for vasoactive intestinal polypeptide. 165 54

Using specific radioimmunoassay and immunocytochemistry for neurokinin A (NKA) and neurokinin B (NKB), distribution and localization of the two peptides in human peripheral tissues were studied. Both NKA-like immunoreactivity (NKA-LI) and NKB-like immunoreactivity (NKB-LI) were present in the walls of the gut and gall bladder and in the pancreas. In the gut, the values for NKA-LI were 0.56-35.73 pmol/g wet weight, while those in pancreas and gall bladder were 0.64-0.68 and 0.36 pmol/g wet weight, respectively. The values of NKB-LI were 0.45-2.66 pmol/g wet weight in the gut, 0.93-1.65 pmol/g wet weight in the pancreas, and 0.30 pmol/g wet weight in the gall bladder. The immunocytochemical reactivity to both peptides was localized to ganglia of the submucosal and myenteric nerve plexuses in the gut wall, and to neurons in the muscle layer and mucosa of the gut wall. Weak but positive NKA-LI appeared in nerve cells of the pancreas, while NKB-LI was not detectable in the pancreas. Conversely, in the gall bladder wall, NKA-LI was undetectable while a very faint NKB-LI was found in the muscle layer. The localization of NKA corresponded closely to that of NKB in the tissues although the relative concentrations of the peptides varied from organ to organ.
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PMID:Distribution of neurokinin A-like and neurokinin B-like immunoreactivity in human peripheral tissues. 166 86

Endocrine cells in the gastrointestinal tract of the domestic duck were identified immunocytochemically using antisera specific to bombesin, chromogranin A, cholecystokinin (CCK), gastrin, glucagon, neuron specific enolase (NSE), neurotensin, secretin, 5-hydroxytryptamine (5-HT), somatostatin, substance P and vasoactive intestinal polypeptide (VIP). Chromogranin A, 5-HT and somatostatin immunoreactive cells were widespread throughout the gastrointestinal tract. Bombesin immunoreactive cells were observed only in the proventriculus and the gizzard. CCK, substance P and neurotensin immunoreactive cells were present in the intestinal tracts from the duodenum to the colorectum. The latter were numerous also in the antrum. Gastrin cells were peculiar to the antrum but present also in the gizzard and small intestine. Glucagon immunoreactive cells were present in the jejunum-ileum and above all in the large intestine. Only few secretin cells were present in the duodenum. The highest frequency of endocrine cells was found in the antrum, while the lowest was observed in the caeca. Antisera to somatostatin and substance P showed numerous nerve cells and fibers besides endocrine cells, whereas NSE and VIP immunopositivity was found in the nervous structures only of the gut wall.
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PMID:An immunohistochemical study on the endocrine cells in the gastrointestinal tract of domestic duck. 168 96

Primary afferent nerve terminals located in the mammalian gut wall may play a role in region-specific modulation of gastrointestinal motility. In the present study, we sought to characterize the effect of neuropeptides released from these afferents by capsaicin (CAP) on contractile activity of smooth muscle from the distal rabbit colon. CAP caused a release of acetylcholine and immunoreactivity for substance P (SP) and calcitonin gene-related peptide (CGRP) from the muscle coat. CAP caused a dose-dependent transient stimulation of longitudinal muscle contractions, followed by prolonged inhibition of spontaneous but not stimulated contractile activity. The initial stimulation was abolished by the SP antagonist spantide and by atropine. The inhibitory effect was reduced by repeated exposure of muscle to CGRP. The effect of CGRP on spontaneous contractions differed between longitudinal and circular muscle. In longitudinal muscle, a stimulation was preceded by a transient inhibition, whereas in circular muscle, only inhibition was seen. Both effects were resistant to tetrodotoxin. Repeated exposure of circular but not longitudinal muscle to CGRP resulted in a disappearance of the peptide's inhibitory effect. Exogenously applied CGRP was only a weak antagonist of contractions stimulated by SP and bethanechol. These findings suggest that in the rabbit colon at least the following two neuropeptides are released from CAP-sensitive nerve fibers: a neurokinin peptide from nerve terminals located within the myenteric plexus and CGRP from terminals probably located within the circular muscle layer.
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PMID:Substance P and CGRP mediate motor response of rabbit colon to capsaicin. 170 Jun 28

NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, markedly enhanced tonic ("hump") responses to transmural stimulation in guinea pig ileum longitudinal muscle. The enhancement of the hump responses was probably due to a prejunctional effect on substance P-like neurotransmission, since the action of L-NMMA was exerted also in the presence of atropine, and since responses to substance P, a mimic of nerve stimulation, were unaffected by L-NMMA as were cholinergic twitch responses and the overflow of [3H]choline. Further in support, the hump responses were blocked by the substance P antagonist Spantide. All effects of L-NMMA were stereospecifically reversed by L-arginine. Endogenous nitric oxide thus selectively modulates peptidergic neurotransmission in the gut.
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PMID:Modulation of autonomic neuroeffector transmission by nitric oxide in guinea pig ileum. 170 30

Substance P-like immunoreactivity in the alimentary canal of the frog Rana esculenta L. was studied by means of the indirect immunoperoxidase method. In all segments of the gastrointestinal tract, immunoreactivity was revealed in both the myenteric and the submucosa plexus. Stained nerve cells were observed in the myenteric plexus but not in the submucous plexus. The proximal part of the oesophagus and hindgut were free of immunoreactive perkarya. The stained nerve cells were of the Dogiel type I category in the foregut, and type II in the midgut. Both the musculature and gastrointestinal glands were supplied with immune-positive fibres. These results indicate that substance P may play similar roles in the frog gut, as described previously in mammals and fish.
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PMID:Distribution of substance p-like immunoreactivity in nerves of the gastrointestinal tract of the frog Rana esculenta L. 170 52

The possible trophic influence of the capsaicin-sensitive extrinsic innervation of the gastrointestinal mucosa was investigated. Rats were treated neonatally with capsaicin. The gastrointestinal content of serotonin and glucagon-like immunoreactivity were used as a measure of the effect on the endocrine gut mucosa and gastrointestinal aminopeptidase and alkaline phosphatase activities were used as a measure of the effect on the gut brush-border. The gastrointestinal content of the neuropeptides substance P, VIP and CGRP were used to monitor effects on the innervation of the gut. The depletion of substance P-immunoreactivity(-IR) and calcitonin gene-related peptide(CGRP)-IR in extracts of urinary bladder and lung from the capsaicin-treated rats is evidence of the efficacy of capsaicin treatment in affecting a loss of C-fibre sensory nerves. The significant depletion of CGRP-IR measured in the stomach and duodenum of capsaicin-treated rats indicated the loss of the C-fibre sensory innervation to the gastrointestinal tract. The gastrointestinal content of VIP and substance P, which are predominantly within intrinsic gut neurones, were unaffected by capsaicin treatment. In all regions of the gastrointestinal tract of capsaicin-treated rats, the serotonin and glucagon-IR levels were not significantly different from those in controls. Similarly the levels of activity of the brush-border enzymes were not significantly effected by capsaicin treatment. This suggest the absence of any major trophic influence of capsaicin-sensitive sensory nerves on the gut endocrine mucosa and the brush border.
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PMID:Regulatory peptide and serotonin content and brush-border enzyme activity in the rat gastrointestinal tract following neonatal treatment with capsaicin; lack of effect on epithelial markers. 170 47

In a pilot study previously reported, we showed that individual nerves could be traced in the different layers of the gut in Hirschsprung's disease (HD) using wholemount immunohistochemistry (WI). Little is known about the course of the important nonadrenergic, noncholinergic nerves containing neuropeptides in HD. Therefore, we studied the distribution of neuropeptides in 9 HD patients and 5 controls using WI. The new findings include the following: (1) there were two populations of substance P (SP) nerves--in aganglionic gut, SP-efferent nerves were decreased but SP-afferent fibres innervating blood vessels and mucosa remained unchanged; (2) met-enkephin was present only in efferent nerves to muscle and was decreased in aganglionic gut; and (3) peptidergic nerves have a disorganised pattern in HD affecting not only aganglionic gut but also "normal" gut at the colostomy site. These peptidergic abnormalities may play an important role in the pathophysiology of HD. In particular, the imbalance of afferent and efferent innervation, a finding not previously described in HD, warrants special attention in future studies.
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PMID:New insights into peptidergic abnormalities in Hirschsprung's disease by wholemount immunohistochemistry. 171 36

Direct regulatory control of the immune system by the central nervous system has been postulated. In support of this view is a large body of literature describing immunoregulatory activities of neuropeptides isolated from the gastrointestinal tract. In this review we examine the evidence for expression of specific receptors for gut peptides on immune effector cells and further explore the regulatory effects of these peptides on immune function. Peptides to be discussed include substance P, somatostatin, vasoactive intestinal peptide (VIP), the opioid peptides leu and met enkephalin, calcitonin gene related peptide (CGRP), neuropeptide Y, and cholecystokinin (CCK).
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PMID:Modulation of immune function by intestinal neuropeptides. 171 37


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