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)

Neural plasticity is not only the adaptive response of the central nervous system to learning, structural damage or sensory deprivation, but also an increasingly recognized common feature of the gastrointestinal (GI) nervous system during pathological states. Indeed, nearly all chronic GI disorders exhibit a disease-stage-dependent, structural and functional neuroplasticity. At structural level, GI neuroplasticity usually comprises local tissue hyperinnervation (neural sprouting, neural, and ganglionic hypertrophy) next to hypoinnervated areas, a switch in the neurochemical (neurotransmitter/neuropeptide) code toward preferential expression of neuropeptides which are frequently present in nociceptive neurons (e.g., substance P/SP, calcitonin-gene-related-peptide/CGRP) and of ion channels (TRPV1, TRPA1, PAR2), and concomitant activation of peripheral neural glia. The functional counterpart of these structural alterations is altered neuronal electric activity, leading to organ dysfunction (e.g., impaired motility and secretion), together with reduced sensory thresholds, resulting in hypersensitivity and pain. The present review underlines that neural plasticity in all GI organs, starting from esophagus, stomach, small and large intestine to liver, gallbladder, and pancreas, actually exhibits common phenotypes and mechanisms. Careful appraisal of these GI neuroplastic alterations reveals that--no matter which etiology, i.e., inflammatory, infectious, neoplastic/malignant, or degenerative--neural plasticity in the GI tract primarily occurs in the presence of chronic tissue- and neuro-inflammation. It seems that studying the abundant trophic and activating signals which are generated during this neuro-immune-crosstalk represents the key to understand the remarkable neuroplasticity of the GI tract.
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PMID:Neural plasticity in the gastrointestinal tract: chronic inflammation, neurotrophic signals, and hypersensitivity. 2341 35

Capsaicin, the pungent component of chilli pepper, stimulates TRPV1-expressing cells which are followed by desensitisation to subsequent exposure to capsaicin and other TRPV1 activators. At high systemic doses (>125 mg/kg), capsaicin produces long-term changes in both tachykinin receptor and TRPV1 expression and function in rats. However, whether desensitising (low) doses of capsaicin (~50 mg/kg) affect tachykinin receptor and TRPV1 gene expression in the short term has yet to be investigated. The aim of the present study was to compare tachykinin receptor (NK1, NK2 and NK3) and TRPV1 mRNA expression 24h after administration of capsaicin (50 mg/kgs.c.). Tachykinin receptor and TRPV1 mRNA were detected in all tissues studied with expression levels differing by up to 2500-fold between tissues. The highest expression of TRPV1 and NK1 mRNA was observed in the salivary gland, whereas NK2 mRNA expression was highest in the urinary bladder and NK3 mRNA expression in the frontal cortex. In the cervical spinal cord of rats treated with capsaicin, NK1 and NK3 mRNA expression were reduced by 56% and 80%, respectively (P<0.05), whereas NK2 and TRPV1 mRNA expression were increased 2.2- and 1.4-fold, respectively (P<0.05). NK1 and NK2 mRNA expression were decreased (P<0.05) in the urinary bladder and gastric fundus, respectively, following capsaicin treatment. There was a marked 100-fold increase in cFOS mRNA expression and 100-fold decrease in NK2 mRNA expression in the whole blood of capsaicin-treated rats. In conclusion, these studies show that tachykinin receptor and TRPV1 mRNA expression undergo significant changes within 24h of systemic low-dose capsaicin administration.
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PMID:Tachykinin (NK1, NK2 and NK3) receptor, transient receptor potential vanilloid 1 (TRPV1) and early transcription factor, cFOS, mRNA expression in rat tissues following systemic capsaicin treatment. 2349 99

Allergic contact dermatitis is a common skin disease associated with inflammation and persistent pruritus. Transient receptor potential (TRP) ion channels in skin-innervating sensory neurons mediate acute inflammatory and pruritic responses following exogenous stimulation and may contribute to allergic responses. Genetic ablation or pharmacological inhibition of TRPA1, but not TRPV1, inhibited skin edema, keratinocyte hyperplasia, nerve growth, leukocyte infiltration, and antihistamine-resistant scratching behavior in mice exposed to the haptens, oxazolone and urushiol, the contact allergen of poison ivy. Hapten-challenged skin of TRPA1-deficient mice contained diminished levels of inflammatory cytokines, nerve growth factor, and endogenous pruritogens, such as substance P (SP) and serotonin. TRPA1-deficient sensory neurons were defective in SP signaling, and SP-induced scratching behavior was abolished in Trpa1(-/-) mice. SP receptor antagonists, such as aprepitant inhibited both hapten-induced cutaneous inflammation and scratching behavior. These findings support a central role for TRPA1 and SP in the integration of immune and neuronal mechanisms leading to chronic inflammatory responses and pruritus associated with contact dermatitis.
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PMID:TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis. 2372 16

Small-fiber neuropathy was induced in young adult mice by intraperitoneal injection of resiniferatoxin (RTX), a TRPV1 agonist. At day 7, RTX induced significant thermal and mechanical hypoalgesia. At day 28, mechanical and thermal nociception were restored. No nerve degeneration in skin was observed and unmyelinated nerve fiber morphology and density in sciatic nerve were unchanged. At day 7, substance P (SP) was largely depleted in dorsal root ganglia (DRG) neurons, although calcitonin gene-related peptide (CGRP) was only moderately depleted. Three weeks after, SP and CGRP expression was restored in DRG neurons. At the same time, CGRP expression remained low in intraepidermal nerve fibers (IENFs) whereas SP expression had improved. In summary, RTX induced in our model a transient neuropeptide depletion in sensory neurons without nerve degeneration. We think this model is valuable as it brings the opportunity to study functional nerve changes in the very early phase of small fiber neuropathy. Moreover, it may represent a useful tool to study the mechanisms of action of therapeutic strategies to prevent sensory neuropathy of various origins.
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PMID:A reversible functional sensory neuropathy model. 2479 90

Spinal sensory neurons innervating visceral and mucocutaneous tissues have unique microanatomic distribution, peripheral modality, and physiological, pharmacological, and biophysical characteristics compared with those neurons that innervate muscle and cutaneous tissues. In previous patch-clamp electrophysiological studies, we have demonstrated that small- and medium-diameter dorsal root ganglion (DRG) neurons can be subclassified on the basis of their patterns of voltage-activated currents (VAC). These VAC-based subclasses were highly consistent in their action potential characteristics, responses to algesic compounds, immunocytochemical expression patterns, and responses to thermal stimuli. For this study, we examined the VAC of neurons retrogradely traced from the distal colon and the glans penis/distal urethra in the adult male rat. The afferent population from the distal colon contained at least two previously characterized cell types observed in somatic tissues (types 5 and 8), as well as four novel cell types (types 15, 16, 17, and 18). In the glans penis/distal urethra, two previously described cell types (types 6 and 8) and three novel cell types (types 7, 14, and 15) were identified. Other characteristics, including action potential profiles, responses to algesic compounds (acetylcholine, capsaicin, ATP, and pH 5.0 solution), and neurochemistry (expression of substance P, CGRP, neurofilament, TRPV1, TRPV2, and isolectin B4 binding) were consistent for each VAC-defined subgroup. With identification of distinct DRG cell types that innervate the distal colon and glans penis/distal urethra, future in vitro studies related to the gastrointestinal and urogenital sensory function in normal as well as abnormal/pathological conditions may be benefitted.
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PMID:Distinct subclassification of DRG neurons innervating the distal colon and glans penis/distal urethra based on the electrophysiological current signature. 2487 31

To investigate neurochemical changes associated with bortezomib-induced painful peripheral neuropathy (PN), we examined the effects of a single-dose intravenous administration of bortezomib and a well-established "chronic" schedule in a rat model of bortezomib-induced PN. The TRPV1 channel and sensory neuropeptides CGRP and substance P (SP) were studied in L4-L5 dorsal root ganglia (DRGs), spinal cord, and sciatic nerve. Behavioral measures, performed at the end of the chronic bortezomib treatment, confirmed a reduction of mechanical nociceptive threshold, whereas no difference occurred in thermal withdrawal latency. Western blot analysis showed a relative increase of TRPV1 in DRG and spinal cord after both acute and chronic bortezomib administration. Reverse transcriptase-polymerase chain reaction revealed a decrease of TRPV1 and CGRP mRNA relative levels after chronic treatment. Immunohistochemistry showed that in the DRGs, TRPV1-, CGRP-, and SP-immunoreactive neurons were mostly small- and medium-sized and the proportion of TRPV1- and CGRP-labeled neurons increased after treatment. A bortezomib-induced increase in density of TRPV1- and CGRP-immunoreactive innervation in the dorsal horn was also observed. Our findings show that bortezomib-treatment selectively affects subsets of DRG neurons likely involved in the processing of nociceptive stimuli and that neurochemical changes may contribute to development and persistence of pain in bortezomib-induced PN.
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PMID:Bortezomib treatment produces nocifensive behavior and changes in the expression of TRPV1, CGRP, and substance P in the rat DRG, spinal cord, and sciatic nerve. 2487 63

We tested the hypothesis that 5-aminosalicylic acid (5-ASA) inhibits toxin A-induced generation of colonic leukotriene B4 (LTB4) and toxin A colitis in rats. Isolated colonic segments in anesthetized rats were treated intraluminally with toxin A for 3 hours with or without 30 minutes of pretreatment with either 5-ASA or sulfapyridine and then colonic tissue levels of LTB4 were measured and inflammation was assessed. Separately, sulfasalazine was administered to rats in their drinking water for 5 days, isolated colonic segments were then prepared, toxin A was administered, and inflammation was assessed as before. Pretreatment with 5-ASA inhibited toxin A-induced increased tissue LTB4 concentration in the colon. Sulfasalazine and 5-ASA but not sulfapyridine significantly inhibited toxin A colitis. However, pretreatment with 5-ASA did not protect against direct TRPV1-mediated colitis caused by capsaicin. Toxin A stimulated the release of substance P (SP), and this effect was also inhibited by sulfasalazine and 5-ASA but not by sulfapyridine. Thus, toxin A stimulates colonic LTB4 resulting in activation of TRPV1, release of SP, and colitis. Inhibition of 5-LO by 5-ASA disrupts this pathway and supports the concept that LTB4 activation of TRPV1 plays a role in toxin A colitis.
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PMID:5-Aminosalicylic Acid Inhibits Acute Clostridium difficile Toxin A-Induced Colitis in Rats. 2504 74

Besides the involvement of TRPV channels in exhibiting various cellular functions including thermoregulation, pain perception, maintenance of bone homeostasis and gastrointestinal function; certain studies have also implicated the putative role of these channels in mediating ischemic conditioning-induced cardioprotection. The potential role of TRPV1 channels in different forms of ischemic conditioning (pre/post/remote)-induced cardioprotection has been described by employing TRPV1 knockout mice and various pharmacological modulators. The cardioprotective effects of TRPV1 activation during ischemic conditioning have been linked with increased CGRP, substance P release and augmented ALOX expression. Furthermore, the role of TRPV4 channels in mediating preconditioning-induced preservation of vascular function in terms restoring NO- and further improving EDH(F)-mediated endothelial relaxation has been described. The present review discusses the putative role of TRPV1 and TRPV4 channels in mediating different forms of conditioning (pre/post/remote)-induced cardioprotection along with the possible mechanisms. Future perspectives have also been described to fully understand the cascade of signaling and contribution of TRPV channel activation during myocardial ischemic conditioning.
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PMID:TRPV1 and TRPV4 channels: potential therapeutic targets for ischemic conditioning-induced cardioprotection. 2544 39

The aim of this study was to investigate the effects of Lactobacillus fermentum Suo (LF-Suo) on activated carbon-induced constipation in ICR (Institute of Cancer Research) mice. ICR mice were orally administered with lactic acid bacteria for 9 days. Body weight, diet intake, drinking amount, defecation status, gastrointestinal transit and defecation time, and the serum levels of MTL (motilin), Gas (gastrin), ET (endothelin), SS (somatostatin), AChE (acetylcholinesterase), SP (substance P), VIP (vasoactive intestinal peptide) were used to evaluate the preventive effects of LF-Suo on constipation. Bisacodyl, a laxative drug, was used as a positive control. The normal, control, 100 mg/kg bisacodyl treatment, LB (Lactobacillus bulgaricus)-, LF-Suo (L)- and LF-Suo (H)-treated mice showed the time to the first black stool defecation at 90, 218, 117, 180, 155 and 137 min, respectively. By the oral administration of LB-, LF-Suo (L), LF-Suo (H) or bisacodyl (100 mg/kg), the gastrointestinal transit was reduced to 55.2%, 72.3%, 85.5% and 94.6%, respectively, of the transit in normal mice, respectively. In contrast to the control mice, the serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Suo (p < 0.05). By the RT-PCR (reverse transcription-polymerase chain reaction) and western blot assays, LF-Suo increased the c-Kit, SCF (stem cell factor), GDNF (glial cell line-derived neurotrophic factor) and decreased TRPV1 (transient receptor potential vanilloid 1), NOS (nitric oxide synthase) expressions of small intestine tissue in mice. These results demonstrate that lactic acid bacteria has preventive effects on mouse constipation and LF-Suo demonstrated the best functional activity.
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PMID:Therapeutic effect of activated carbon-induced constipation mice with Lactobacillus fermentum Suo on treatment. 2546 78

Capsaicin, the pungent alkaloid of red pepper (Capsicum annuum) has been extensively studied for its biological effects which are of pharmacological relevance. These include: cardio protective influence, antilithogenic effect, antiinflammatory, and analgesia, thermogenic influence, and beneficial effects on gastrointestinal system. Therefore, capsaicinoids may have the potential clinical value for pain relief, cancer prevention and weight loss. It has been shown that capsaicinoids are potential agonists of capsaicin receptor (TRPV1). They could exert the effects not only through the receptor-dependent pathway but also through the receptor-independent one. The involvement of neuropeptide Substance P, serotonin, and somatostatin in the pharmacological actions of capsaicin has been extensively investigated. Topical application of capsaicin is proved to alleviate pain in arthritis, postoperative neuralgia, diabetic neuropathy, psoriasis, etc. Toxicological studies on capsaicin administered by different routes are documented. Capsaicin inhibits acid secretion, stimulates alkali and mucus secretion and particularly gastric mucosal blood flow which helps in prevention and healing of gastric ulcers. Antioxidant and antiinflammatory properties of capsaicin are established in a number of studies. Chemopreventive potential of capsaicin is evidenced in cell line studies. The health beneficial hypocholesterolemic influence of capsaicin besides being cardio protective has other implications, viz., prevention of cholesterol gallstones and protection of the structural integrity of erythrocytes under conditions of hypercholesterolemia. Beneficial influences of capsaicin on gastrointestinal system include digestive stimulant action and modulation of intestinal ultrastructure so as to enhance permeability to micronutrients.
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PMID:Biological Activities of Red Pepper (Capsicum annuum) and Its Pungent Principle Capsaicin: A Review. 2567 68


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