Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroepithelial bodies (NEB) in 29-day fetal rabbit lung were examined by light microscopy and cytochemistry to demonstrate their structural and biochemical properties in situ. Longitudinal sections of NEB at airway bifurcations demonstrated their chemoreceptor-like appearance. Furthermore, the cytochemical presence of serotonin, acetylcholinesterase, formaldehyde-induced fluorescence, and silver-staining properties demonstrated the neural-like biochemical properties of NEB cells. Forty-one NEB and eight single neuroendocrine cells from whole fetal lungs were examined ultrastructurally. Juxtaluminal junctional complexes composed of tight and intermediate junctions, desmosomes, and cytoplasmic filaments were demonstrated in the corpuscular-shaped NEB. Basal bodies were apparent in NEB cell cytoplasm; cilia extended from NEB cells. Dense-core vesicles (DCV) were of at least three types: type 1, type 2, and enterochromaffin type. The majority of epithelial cells adjacent to NEB in near-term airway epithelium were undifferentiated, with large amounts of glycogen. However, ciliated cells were adjacent to some small NEB and single neuroendocrine cells; mucus or Clara-type cells were not observed. NEB isolated by collagenase treatment revealed an intact organoid structure, DCV, and desmosomes and retained their argyrophilia and formaldehyde-induced fluorescence. NEB were recovered in cell fractions separated by unit gravity that had cells in clumps of four or more. One to five NEB stained with silver in cytocentrifuge preparations of control, mixed cells, whereas up to 20 intact NEB were demonstrated in the clump-containing, separated fractions. We propose that isolated NEB retain certain biochemical and metabolic properties similar to those of their counterparts in situ. Serotonin and 5-hydroxyindole acetic acid were found by high-performance liquid chromatography analysis in the fractions containing NEB, and amine precursor uptake and decarboxylation (APUD) activity were demonstrated. Moreover, muscarinic cholinergic receptors were detected, consistent with the occurrence of acetylcholinesterase in NEB. The elution profile of bombesin radioimmunoactivity substantiated that isolated fetal rabbit NEB contained this neuropeptide and that NEB were enriched by unit gravity sedimentation. These studies suggest that NEB are structurally and functionally developed before other cell types in immature airway epithelium and can be isolated as intact organoids, which retain some of their structural and metabolic integrity.
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PMID:Morphological and cytochemical characterization of neuroepithelial bodies in fetal rabbit lung. I. Studies of isolated neuroepithelial bodies. 613 13

To elucidate the mechanism by which palate shelves reorient during embryogenesis, migration of palate mesenchymal cells has been studied employing various substrates. When palate explants were cultured in a hydrated collagen lattice, it was observed that bipolar spindle-shaped cells migrated out of each explant toward the other. These cells were aligned parallel to each other and to the fibrous tracks that formed. The cells appeared to move along and through the fibrous tracks. Cell migration was dependent on the presence of serum and fibronectin. The fibrous tracks viewed by phase microscopy were sensitive to collagenase. Scanning electron microscopy revealed that the collagen fibers of the hydrated lattice had coalesced into larger bundles. Pretreatment of explants with serotonin stimulated cell migration out of the explant into the hydrated collagen lattice. This effect was specific, since the antagonist methysergide blocked the stimulation produced by serotonin. Employing other substrates, it was noted that palate cells migrating out of double explants toward each other produced large wrinkles in a polysiloxane substratum. Similarly, cultured monolayer cells also produced wrinkles that disappeared as cells rounded up after trypsin treatment. Finally, monolayer cells pulled on and distorted collagen films when cultured on the substrate. It is concluded that migrating palate cells can interact with their substrate producing tractional forces. Serotonin-induced modulation of cell motility and its relationship to palate reorientation are discussed.
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PMID:Palate cell motility and substrate interaction. 635 29

Collagenase (100 micrograms) induced a large plasma extravasation, during the first 15 min after its injection in rat paw, associated with the rapid development of oedema which subsided after 6 h. The extent of the oedema was similar in normal and kininogen-deficient rats. The swelling induced in normal rats was reduced by HOE 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), a bradykinin B2 receptor antagonist, and by three serine protease inhibitors, soybean trypsin inhibitor (SBTI), Leucaena leucocephala trypsin inhibitor 1 (LLTI-1) and Leucaena leucocephala trypsin inhibitor 2 (LLTI-2). These agents had no effect on the oedema induced in kininogen-deficient rats. The swelling was also reduced by methysergide, indomethacin, ketoprofen and methylprednisolone. It was increased by heparin, but it was not modified by mepyramine, WEB 2086 (3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]-triazolo- [4,3-a][1,4]-diazepine-2-yl]-1-(4-morpholinyl)-1-propanone) and NG-nitro-L-arginine. In vitro, collagenase did not release kinins from rat plasma or from purified T-kininogen. LLTI-1 and LLTI-2 did not inhibit collagenase activity for one of its specific substrates. Kinins are thus involved in the development of collagenase oedema in normal rats. Their generation would be indirect following changes in matrix proteins in extravascular spaces. Nevertheless, kinins are not the decisive mediators of the swelling. Serotonin, possibly released from platelets, and prostanoids participate in the inflammatory process.
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PMID:Collagenase-induced oedema in the rat paw and the kinin system. 776 61

Previous studies have shown that the production of interstitial collagenase by rat myometrial smooth muscle cells is dependent on serotonin. These cells fail to produce collagenase early in culture, however, and produce the enzyme only 8-12 days after confluence. During the early quiescent period, collagenase production can be induced by low concentrations of bacterial endotoxin. Under these conditions, interleukin (IL)-1 alpha and IL-1 beta mRNAs increase coincident with collagenase and collagenase mRNA. Serotonin removal decreases IL-1 alpha and IL-1 beta mRNAs, and effect that is rapidly reversed upon readdition of serotonin. Conversely, serotonin-dependent increases in IL-1 mRNAs are blocked by progesterone. Experiments with 5-HT2 receptor agonists and antagonists indicate that induction is mediated by the 5-HT2 receptor subtype. In serotonin-treated cells late in culture, IL-1 mRNAs increase coincident with the production of collagenase. Similarly, exogenous IL-1 fully substitutes for lipopolysaccharide in stimulating myometrial cells to produce collagenase early in culture. Cells treated with IL-1 receptor antagonist fail to make IL-1 mRNAs or collagenase but produce collagenase and IL-1 mRNAs following antagonist removal. These results indicate that serotonin-dependent IL-1 production by the myometrial cell is required for collagenase production and that IL-1 participates in its own production via an autocrine mechanism.
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PMID:Serotonin regulation of interleukin-1 messenger RNA in rat uterine smooth muscle cells. Relationship to the production of interstitial collagenase. 796 54

Serotonin (5-hydroxytryptamine; 5-HT) has recently been shown to induce collagenase production in myometrial smooth muscle cells (Jeffrey et al. (1991) J. Cell. Physiol. 146, 399-406) by activating transcription of the collagenase gene (Wilcox et al. (1992) J. Biol. Chem. 267, 20752-20757) following an interaction with the 5-HT2 receptor (Rydelek-Fitzgerald et al. (1993) Mol. Cell. Endocrinol. 91, 67-74). These studies were performed to investigate factors controlling the regulation of 5-HT2 receptors in these cells. Northern blot analysis indicates that serotonin increases levels of 5-HT2 receptor mRNA in cells by approximately 4-fold. Detectable increases in mRNA levels occur within 2 h after administration of serotonin with maximal levels occurring after 12 h. The 5-HT2 receptor antagonists, ketanserin and spiperone, inhibit the serotonin-mediated increase in receptor mRNA. Selective 5-HT2 receptor agonists ((+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) and quipazine) mimic the effect of serotonin, whereas 5-HT1 and 5-HT3 receptor agonists ((+/-)-8-hydroxydipropylaminotetralin (8-OH-DPAT), 1-(3-chlorophenyl)piperazine dihydrochloride (mCPP), m-phenylbiguanide) have no effect. These data demonstrate that serotonin induces an increase in 5-HT2 receptor mRNA by interacting with the 5-HT2 receptor itself. Nuclear run-on analysis revealed that serotonin increases the initiation of 5-HT2 receptor mRNA synthesis. Moreover, the protein synthesis inhibitor, cycloheximide, prevents the induction of the mRNA for the receptor, demonstrating that serotonin-dependent increases in 5-HT2 receptor transcription require de novo protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin-mediated 5-HT2 receptor gene regulation in rat myometrial smooth muscle cells. 831 29

Experiments were designed to determine the viability of endothelial cells and their responses to products released by aggregating platelets following single flush perfusion of the coronary arteries with cardioplegic solutions used for cardiac transplantation. Porcine coronary arteries were perfused with crystalloid (Plegisol) or blood cardioplegic solutions; nonperfused hearts placed in 0.9% saline were used as controls. Immediately following perfusion and after 5-hour storage of the hearts in the same cardioplegic solution, rings were cut from the right coronary arteries and suspended in organ chambers for the measurement of isometric force. In some rings the endothelium was removed deliberately. The left circumflex coronary arteries were flushed with collagenase and the harvested endothelial cells were plated for cell culture. Left anterior descending coronary arteries were perfusion fixed with glutaraldehyde for scanning electron microscopy. In the organ chamber experiments, aggregating platelets and adenosine diphosphate caused relaxations in rings with endothelium. These relaxations were reduced immediately following crystalloid cardioplegia and were restored following 5-hour storage. Serotonin caused contractions in all rings. Rings without endothelium were more sensitive than rings with endothelium to the amine; this difference was augmented following 5-hour storage of the heart. Significantly fewer foci of endothelial cells grew in culture following 5-hour storage of the hearts in crystalloid cardioplegic solution compared to control (p < 0.05). There were no anatomical differences identified among groups by scanning electron microscopy. These results suggest that crystalloid cardioplegia alters the responses of coronary arteries to substances released by aggregating platelets and reduces the ability of endothelial cells to replicate. Such changes may contribute to altered vascular resistance following reperfusion of transplanted hearts and potentially to later structural changes in the coronary arteries.
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PMID:Cardioplegia alters porcine coronary endothelial cell growth and responses to aggregating platelets. 843 71

Recent studies have shown that serotonin (5-hydroxytryptamine; 5-HT) is required for the induction of interstitial collagenase in cultured rat and human myometrial smooth muscle cells. The present study was performed to determine which serotonin receptor subtype mediates the induction of collagenase in these cells. [125I]DOI ((+/- )-1-(2,5-dimethoxy-4-[125I]iodophenyl)-2-aminopropane), a 5-HT2 receptor agonist radioligand, bound specifically to sites in myometrial cell membranes, and exhibited binding characteristics essentially identical to those observed with brain 5-HT2 receptors. Radioligands selective for other serotonin receptor subtypes (5-HT1 and 5-HT3) failed to yield detectable binding. Northern blot analysis demonstrated the presence of 5-HT2 mRNA in the uterine smooth muscle cell cultures, whereas transcripts for 5-HT1A and 5-HT1C receptors were not detectable. Moreover, RT-PCR indicated that 5-HT2 receptor mRNA is present in freshly isolated uterine tissue as well. Selective antagonists of the 5-HT2 receptor, ketanserin and spiperone, displayed concentration-dependent inhibition of serotonin-mediated collagenase induction in the myometrial cultures. These antagonists yielded IC50 values of 4.7 nM and 2.7 nM respectively, characteristic of values expected from a 5-HT2 receptor-mediated response. In addition, a number of selective 5-HT2 receptor agonists (quipazine, alpha-methyl-serotonin, DOI) mimicked the ability of serotonin to induce collagenase production, whereas compounds selective for 5-HT1 and 5-HT3 receptor subtypes had little effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin-dependent collagenase induction in rat myometrial smooth muscle cells: mediation by the 5-HT2 receptor. 847 55

The involvement of bradykinin, 5-hydroxytryptamine, substance P and prostanoids in the hyperalgesia elicited by collagenase in rat paw was investigated. Collagenase (100 micrograms) induced a slight hyperalgesia in kininogen deficient rats in comparison with the behavioural response obtained in normal rats. Lisinopril (10(-5) M), and angiotensin-converting enzyme inhibitor, increased the duration of the hyperalgesia elicited in normal rats. Ondansetron (0.5 to 5 mumol/kg), a 5-HT3 antagonist, suppressed the hyperalgesia as did methysergide (1.1 to 11 mumol/kg), a mixed 5-HT1 and 5-HT2 receptor antagonist. However, the hyperalgesia was not modified by RP 67580 (1.8 to 18 mumol/kg), a NK1 receptor antagonist, and was only slightly delayed by indomethacin (2 mg/kg), a cyclo-oxygenase inhibitor. The oedema-promoting effect of 5-HT (6 nmol) was inhibited by methysergide but not by ondansetron. The swelling induced by collagenase in rat paw was reduced by methysergide but not by ondansetron. We conclude that the behavioural response induced by collagenase depends on an interactions between bradykinin and 5-HT. Prostanoids play a minor role in the beginning of the reaction whereas substance P is not significantly involved in this hyperalgesia.
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PMID:Involvement of 5-hydroxytryptamine and bradykinin in the hyperalgesia induced in rats by collagenase from Clostridium histolyticum. 915 Dec 93

Although serotonin (5-HT) release from enterochromaffin (EC) cells is considered to be regulated by multiple receptor-mediated mechanisms, little is known about the signal transduction in EC cells. We investigated the effects of adrenoceptor stimulation on 5-HT release from ileal tissue and intracellular calcium dynamics of epithelial cells in isolated ileal crypts in mice. Ileal tissues placed in organ bath were perfused with a buffered solution. Released 5-HT was measured using HPLC-ECD. Ileal crypts were isolated by collagenase digestion followed by moderate pipetting. Intracellular calcium dynamics were analyzed by digital video-imaging system using fura-2. NE, but not isoprenaline (Iso), induced 5-HT release from mouse ileal tissue. NE-induced 5-HT release was antagonized by yohimbine and rauwolscine, but not by prazosin and bunazosin. NE, but not Iso, also elicited a transient elevation of intracellular calcium in some EC cells. The effect of NE (1 microM) was slightly suppressed by prazosin and bunazosin, but was remarkably suppressed by yohimbine and rauwolscine. UK 14,304 and Clonidine at 10 microM significantly induced an increase in intracellular calcium concentration. NE-induced intracellular calcium dynamics was not significantly affected by timolol, Ro20-1724, rolipram and 8-bromo-cAMP. These results suggest that NE-induced 5-HT release from ileal EC cells is mediated predominantly via alpha 2-, but not beta-adrenoceptors, by a mechanism dependent on elevation of intracellular calcium concentration.
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PMID:[Signal transduction of serotonin release from enterochromaffin cells in mouse ileal crypts]. 1019 Jan 50

Interleukin-1 has been shown to contribute to infection-induced inflammatory processes during pregnancy. Prior work from this laboratory has demonstrated that serotonin-induced IL-1alpha also is required for the in-vitro production of collagenase in uterine smooth muscle cells, a normal, non-inflammatory process that occurs in-vivo during post-partum uterine involution. To understand the molecular mechanisms that regulate transcription of the IL-1alpha gene in these cells, we isolated and characterized 1.6 kilobases of the 5'-flanking region of the rat IL-1alpha gene. Sequencing and primer extension identified a single transcription start site and multiple potential regulatory elements, including a TATA box at - 30 bp, a CAAT box at - 74 bp, and a conserved AP-1 site at - 9 bp. This 5'-flanking DNA exhibited low basal promoter activity that was inducible by serotonin. Serotonin-induced promoter activity was unaffected or induced by either medroxyprogesterone or IL-1 receptor antagonist. This occurred despite the ability of both of these hormones to markedly decrease IL-1alpha mRNA. Deletional analysis revealed a strong repressor in the region between - 147 and - 98 bp; removal of this sequence resulted in a fivefold higher basal promoter activity that was still serotonin responsive. Constitutive promoter activity appeared to reside between - 97 and - 22 bp. Deletion of this promoter region, which contained the TATA and CAAT boxes and an NF-IL-6/PEA-3 site, resulted in decreased basal transcriptional activity to the low level seen in larger constructs. Mutational analysis showed that serotonin-inducible transcriptional activity was mediated, at least in part, by the conserved AP-1 site at - 9 bp. This site is located within a larger extended palindromic region: 5'-AAGCCTGACTCAGACTT-3', that together effects both the basal and serotonin-inducible expression of the IL-1alpha gene.
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PMID:Serotonin-inducible transcription of interleukin-1alpha in uterine smooth muscle cells requires an AP-1 site: cloning and partial characterization of the rat IL-1alpha promoter. 1043 20


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