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)

In order to investigate the role of neural regulation in corneal epithelial healing, we examined the effect of substance P (SP) on corneal epithelial migration using an organ culture system of rabbit corneas. We investigated the synergistic effects of SP with (1) growth factors: epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta(TGF-beta); (2) extracellular matrix proteins: fibronectin, vitronectin, laminin, and collagen type IV; and (3) cytokines: interleukin-1alpha (IL-1alpha), IL-1beta, and interleukin-6 (IL-6). Rabbit corneal blocks were cultured in the absence or presence of various reagents for 24 hr. The corneal blocks were then fixed, dehydrated, embedded in paraffin and stained by hematoxylin-eosin, and the length of the path of epithelial migration was measured. The addition of SP alone, at concentrations up to 50 microg ml-1, did not affect epithelial migration. EGF, fibronectin, vitronectin, collagen type IV, and IL-6 stimulated epithelial migration, but bFGF, TGF-beta, laminin, IL-1alpha, and IL-1betadid not. The stimulatory effect of EGF on the epithelial migration was enhanced by the presence of SP. This synergistic effect of SP and EGF on corneal epithelial migration was abolished by the addition of an SP antagonist or enkephalinase. Other neurotransmitters (vasoactive intestinal peptide, calcitonin gene-related peptide, acetylcholine chloride, norepinephrine, serotonin) and tachykinins (neurokinin A, neurokinin B, kassinin, eledoisin, physalaemin) were examined, but none exhibited a synergistic effect with EGF. Interestingly, EGF alone stimulated the incorporation of 3H-thymidine into corneal epithelial cells, but the addition of SP with EGF did not enhance this effect. These results demonstrate that SP enhanced the EGF stimulation of corneal epithelial migration in vitro in a specific manner, suggesting a possible role of SP as a modulator of epithelial wound healing.
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PMID:Synergistic effect of substance P with epidermal growth factor on epithelial migration in rabbit cornea. 929 69

The muscle and epithelial tissues of the gallbladder are regulated by a ganglionated plexus that lies within the wall of the organ. Although these ganglia are derived from the same set of precursor neural crest cells that colonize the gut, they exhibit structural, neurochemical and physiological characteristics that are distinct from the myenteric and submucous plexuses of the enteric nervous system. Structurally, the ganglionated plexus of the guinea pig gallbladder is comprised of small clusters of neurons that are located in the outer wall of the organ, between the serosa and underlying smooth muscle. The ganglia are encapsulated by a shell of fibroblasts and a basal lamina, and are devoid of collagen. Gallbladder neurons are rather simple in structure, consisting of a soma, a few short dendritic processes and one or two long axons. Results reported here indicate that all gallbladder neurons are probably cholinergic since they all express immunoreactivity for choline acetyltransferase. The majority of these neurons also express substance P, neuropeptide Y, and somatostatin, and a small remaining population of neurons express vasoactive intestinal peptide (VIP) immunoreactivity and NADPH-diaphorase enzymatic activity. We report here that NADPH-diaphorase activity, nitric oxide synthase immunoreactivity, and VIP immunoreactivity are expressed by the same neurons in the gallbladder. Physiological studies indicate that the ganglia of the gallbladder are the site of action of the following neurohumoral inputs: 1) all neurons receive nicotinic input from vagal preganglionic fibers; 2) norepinephrine released from sympathetic postganglionic fibers acts presynaptically on vagal terminals within gallbladder ganglia to decrease the release of acetylcholine from vagal terminals; 3) substance P and calcitonin gene-related peptide, which are co-expressed in sensory fibers, cause prolonged depolarizations of gallbladder neurons that resemble slow EPSPs; and 4) cholecystokinin (CCK) acts presynaptically within gallbladder ganglia to increase the release of acetylcholine from vagal terminals. Results reported here indicate that hormonal CCK can readily access gallbladder ganglia, since there is no evidence for a blood-ganglionic barrier in the gallbladder. Taken together, these results indicate that gallbladder ganglia are not simple relay stations, but rather sites of complex modulatory interactions that ultimately influence the functions of muscle and epithelial cells in the organ.
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PMID:Innervation of the gallbladder: structure, neurochemical coding, and physiological properties of guinea pig gallbladder ganglia. 932 15

Contractile fibroblasts are believed to be responsible for palmar fascia contracture in Dupuytren's Disease. An in vitro collagen lattice model was used to examine the contractile properties of Dupuytren's fibroblasts from 10 patients undergoing partial fasciectomy, and palmar fascia fibroblasts from 6 patients undergoing carpel tunnel release. Dupuytren's and palmar fascia fibroblasts cultured within a stabilized collagen lattice acquired morphological characteristics similar to those of 'myofibroblasts' in Dupuytren's diseased fascia. Both types of fibroblasts generated contractile forces that resulted in rapid collagen lattice contraction after release of the lattice from points of stabilization. Generation of contractile force by the fibroblasts was inhibited by disruption of the actin cytoskeleton, lack of cells, or serum removal. Afferent neuropeptides (substance P, galanin and neurokinin A) did not promote lattice contraction. These results demonstrate that normal palmar fascia fibroblasts can modulate into Dupuytren's-like fibroblasts and that cultured fibroblasts, from either Dupuytren's diseased or normal palmar fascia, can generate contractile forces that are transmitted to extracellular matrix. In addition, fibroblast contraction is an actin based process which requires specific factor(s) present in serum. It is suggested that in Dupuytren's disease extracellular cues trigger the modulation of fibroblasts to Dupuytren's fibroblasts and the promotion of contractile forces responsible for palmar fascia contrature.
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PMID:Generation of contractile force by cultured Dupuytren's disease and normal palmar fibroblasts. 943 48

Anastomotic leakage is the main reason of high mortality in colorectal surgery. The healing of anastomosis is predominantly derived from collagen fibrils. Substance P causes the proliferation of fibroblasts and connective tissue. The effect of SP on postoperative changes of collagen concentration was measured around the anastomotic side in rats. The studies shows, that SP induces a significant decrease in collagen synthesis in colon.
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PMID:[The effect of substance P on collagen concentration in rat colon]. 952 83

Pain management for partial-thickness burns and split-thickness skin graft donor sites remains a persistent problem. Topical capsaicin (trans-b-methyl-N-vanillyl-noneamide) has been successful for pain relief in postherpetic neuralgia, arthritis, and diabetic neuropathy. It is thought to work by inhibiting type C cutaneous factors and by releasing substance P, which is essential for wound healing. To evaluate the effects of topical capsaicin treatment on burn wounds and donor sites, an in vitro study was designed to consider cytotoxic effects of commercial concentrations of capsaicin on keratinocytes and fibroblasts. Human keratinocytes and human fibroblasts were grown in tissue culture and exposed to varying concentrations of capsaicin (0.025% weight/volume to 0.2% weight/volume). In addition, fibroblast-seeded collagen matrixes were exposed to capsaicin to evaluate the compound's ability to cause cytotoxic effects beneath the surface. Keratinocyte growth was reduced 21% to 31% in commercial concentrations of capsaicin 0.025% to 0.20% weight/volume. Fibroblasts were reduced 5% to 10% during the first 6 hours of exposure to capsaicin and 30% after 24 hours across the full range of concentrations tested. At concentrations of at least 0.1% weight/volume, capsaicin penetrated the collagen matrixes, resulting in fibroblast degeneration not only on the surface but also in the inner layers. On the basis of the fact that capsaicin was demonstrated to be cytotoxic to keratinocytes and fibroblasts and on the basis of its known detrimental effect on wound healing, it does not appear that topical capsaicin is indicated for the treatment of burns.
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PMID:Toxic effects of capsaicin on keratinocytes and fibroblasts. 978 76

In the endothelium-denuded arteries cultured in the presence of FBS, morphological (i.e. smooth muscle disorientation and increase in collagen fiber) and phenotypic changes in smooth muscle were observed. Correlated with these changes, contractile force induced by high concentration of KCl and norepinephrine was significantly decreased. In addition, Ca-induced contraction in the permeabilized muscle was also significantly reduced. The reduced contractility in the FBS-treated arteries was partially recovered by the treatment with L-NMMA. In the endothelium-intact arteries cultured in the presence of FBS or PDGF, substance P and ionomycin-mediated, endothelium-dependent relaxation (EDR) was significantly decreased compared to the arteries cultured in serum-free condition. In addition, amounts of NO production and total recoverable eNOS mRNA was reduced in the FBS and PDGF-treated arteries. In these arteries, however, cGMP-dependent relaxation in smooth muscle was not impaired. These results suggest that long-term treatment of vascular tissue with growth-activating agents causes morphological or phenotypic changes nad up-regulation of NO production in smooth muscle, resulting in a reduced contractility. Furthermore, longterm treatment with these agents impairs NO-mediated EDR by decreasing eNOS mRNA and NO production.
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PMID:[Long-term effects of growth-activating agents on smooth muscle contraction and endothelial function in organ-cultured rabbit mesenteric artery]. 1019 Jan 36

Three-month-old male rats were subjected 3 times weekly for 1 h to eccentric exercise of one triceps surae muscle (30 stimulations/min) under general anesthesia in order to induce Achilles tendon disorder corresponding to paratenonitis and tendinosis in man. Net muscle work during the sessions ranged between 0.67 and 4.37 mJ (mean 1.72, SD 0.77). After 9 and 13 sessions, respectively, 2 rats started to show gait alterations during the functional test which was performed 2-3 times weekly. These rats were killed after additional sessions which showed a worsening of the limp. The other trained rats and controls did not limp and were killed after 7-11 weeks. Histologic evaluation of the Achilles tendons from the exercised limb showed in the majority of the cases hypervascularization, increased number of nerve filaments and increased immunoreactivity for substance P and calcitonin gene-related peptide. The tendons from the nonstimulated limb looked normal. The distribution of collagen types I and II appeared normal in the tendon and its insertion to the calcaneus. Inflammation of the epi- and paratenon could be provoked in the rat, but tendon changes corresponding to chronic tendinosis did not develop within 11 weeks with the used training regime. The clinical relevance of this model for chronic tendon disease needs to be evaluated further.
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PMID:Rat model of Achilles tendon disorder. A pilot study. 1046 Sep 71

We studied the effect of recombinant human interleukin-11 (rhIL-11), a cytokine with protective effects against injury to the intestinal mucosa, on inflammatory changes in the muscle layers of the gut, in rabbits with colitis. A single dose of rhIL-11 (4, 40, or 720 microg/kg) was given 1 h before colitis was induced with 135 mg/kg 2, 4,6-trinitrobenzene sulfonic acid (TNBS), followed by a continuous s. c. administration of 4, 40, or 720 microg/kg. day rhIL-11 or saline for 5 days. Colitis affected mucosal architecture, general mechanical properties (passive tension increased with 12.3 g/mm(2), optimal stretch decreased with 26%), and collagen content (decreased from 366 +/- 25 to 237 +/- 13 microg/mg of protein). Changes in passive tension and collagen content were normalized by the highest and lowest dose of rhIL-11, respectively, but neither dose could normalize the optimal stretch. Colitis also decreased maximal contractile tension in response to acetylcholine (ACh), motilin, substance P (SP), K(+), and prostaglandin E(2) but this was normalized with 40 microg/kg. day (motilin, SP) and 720 microg/kg. day (ACh, K(+)) rhIL-11 but not for prostaglandin E(2). For motilin and SP, receptor density was decreased in colitis and normalized in treated rabbits. Colitis also increased the contractile potency toward ACh, an effect already reversed by rhIL-11, 4 microg/kg. day. In conclusion, rhIL-11 partially normalizes disturbed tension generation in experimental colitis. The use of this cytokine in the treatment of irritable bowel disease may contribute to the restoration of motor dysfunction.
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PMID:Dose-dependent effects of recombinant human interleukin-11 on contractile properties in rabbit 2,4,6-trinitrobenzene sulfonic acid colitis. 1094 50

We investigated the muscular structure and innervation of the gastroduodenal junction in the guinea pig. In the gastroduodenal junction, the innermost layer of the circular muscle contained numerous nerve fibers and terminals. Since this nerve network continued onto the deep muscular plexus (DMP) of the duodenum, we surmised that the numerous nerve fibers in the gastroduodenal junction were specialized DMP in the most proximal part of the duodenum. The innermost layer containing many nerve fibers was about 1,000 microm in length and 100 microm in thickness in the proximal duodenum. This layer contained numerous connective tissue fibers composed of collagen and elastic fibers. Five to 30 smooth muscle cells lay in contact with each other and were surrounded by fine connective tissue. The nerve fibers in the proximal duodenum contained nerve terminals immunoreactive for choline acetyltransferase, dynorphin, enkephalin, galanin, gastrin-releasing peptide, nitric oxide synthase, substance P, and vasoactive intestinal polypeptide. Adrenergic fibers which contained tyrosine hydroxylase immunoreactivity were rare in the proximal duodenum. In the innermost layer of the proximal duodenum, there were numerous c-Kit immunopositive cells that were in contact with nerve terminals. This study allowed us to clarify the specific architecture of the most proximal portion of the duodenum. The functional significance of the proximal duodenum in relation to the electrical connection and neural cooperation of the musculature between the antrum and the duodenum is also discussed.
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PMID:Muscular innervation of the proximal duodenum of the guinea pig. 1107 65

Vascular resistance in the mammalian pulmonary circulation is affected by many endogenous agents that influence vascular smooth muscle, right ventricular myocardium, endothelial function, collagen and elastin deposition, and fluid balance. When the balance of these agents is disturbed, e.g. by airway hypoxia from high altitude or pulmonary obstructive disorders, pulmonary hypertension ensues, as characterized by elevated pulmonary artery pressure (P(PA)). Among neuropeptides with local pulmonary artery pressor effects are endothelin-1 (ET-1), angiotensin II (AII), and substance P, and among mitigating peptides are calcitonin gene-related peptide (CGRP), adrenomedullin (ADM), atrial natriuretic peptide (ANP), vasoactive intestinal peptide (VIP) and ET-3. Moreover, somatostatin28 (SOM28) exacerbates, whereas SOM14 decreases P(PA) in hypoxic rats, with lowering and increasing of lung CGRP levels, respectively. Pressure can also be modulated by increasing or decreasing plasma volume (VIP and ANP, respectively), or by induction or suppression of vascular tissue remodeling (ET-1 and CGRP, respectively). Peptide bioavailability and potency can be regulated through hypoxic up- and down- regulation of synthesis or release, activation by converting enzymes (ACE for AII and ECE for ET-1), inactivation by neutral endopeptidase and proteases, or by interaction with nitric oxide (NO). Moreover, altered receptor density and affinity can account for changed peptide efficacy. For example, upregulation of ET(A) receptors and ET-1 synthesis occurs in the hypoxic lung concomitantly with reduced CGRP release. Also, receptor activity modifying protein 2 (RAMP2) has been shown to confer ADM affinity to the pulmonary calcitonin-receptor-like receptor (CRLR). We recently detected the mRNA encoding for RAMP2, CRLR, and the CGRP receptor RDC-1 in rat lung. The search for an effective, lung selective treatment of pulmonary hypertension will likely benefit from exploring the imbalance and restoring the balance between these native modulators of intrapulmonary pressure. For example, blocking of the ET-1 receptor ET(A) and vasodilation by supplemental CGRP delivered i. v. or via airway gene transfer, have proven to be useful experimentally.
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PMID:The role of endogenous lung neuropeptides in regulation of the pulmonary circulation. 1119 57


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