Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Amphibian myelinated nerve fibers were treated with collagenase and protease. Axons with retraction of the myelin sheath were patch-clamped in the nodal and paranodal region. One type of Na channel was found. It has a single-channel conductance of 11 pS (15 degrees C) and is blocked by tetrodotoxin. Averaged events show the typical activation and inactivation kinetics of macroscopic Na current. Three potential-dependent K channels were identified (I, F, and S channel). The I channel, being the most frequent type, has a single-channel conductance of 23 pS (inward current, 105 mM K on both sides of the membrane), activates between -60 and -30 mV, deactivates with intermediate kinetics, and is sensitive to dendrotoxin. The F channel has a conductance of 30 pS, activates between -40 and 60 mV, and deactivates with fast kinetics. The former inactivates within tens of seconds; the latter inactivates within seconds. The third type, the S channel, has a conductance of 7 pS and deactivates slowly. All three channels can be blocked by external tetraethylammonium chloride. We suggest that these distinct K channel types form the basis for the different components of macroscopic K current described previously.
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PMID:Single-channel recording in myelinated nerve fibers reveals one type of Na channel but different K channels. 255 Sep 37

The three-dimensional morphology of the surface of myelinated nerve fibres in the mouse sciatic nerve was studied by scanning electron microscopy after combined potassium hydroxide treatment and collagenase digestion (to remove the surrounding collagen fibrils and basal laminae from nerve fibres) as well as by transmission electron microscopy. The myelinated nerve fibre appeared as a long cylinder with sporadic annular constrictions corresponding to the nodes of Ranvier. Slight swellings of the surface due to Schwann cell nuclei were usually found at the middle of each internode. The surface of the nerve fibre clearly exhibited a network of bulges, which consisted of longitudinal bands extending from the nuclear swelling to the nodes of Ranvier through the internode, and transverse trabeculae bridging between these longitudinal bands. These bulges on the surface of nerve fibres were the site of the retained Schwann cell cytoplasm external to the myelin lamellae. These cytoplasmic networks on myelinated fibres presumably corresponded to the networks described by Cajal following silver impregnation. In addition, other thin elevations and focal round swellings were also found associated with these longitudinal bands and transverse trabeculae. These networks of Schwann cell cytoplasm are considered to be cytoplasmic channels for nutrition. The two apposing paranodal bulbs of nodes of Ranvier were often asymmetrical in their structure. The networks of the paranodal region were more complicated than those in the internode. The networks of Schwann cell cytoplasm converged into a continuous circumferential collar toward the node, which in turn gave rise to finger-like projections into the nodal gap.
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PMID:Scanning electron microscopic studies of the myelinated nerve fibres of the mouse sciatic nerve with special reference to the Schwann cell cytoplasmic network external to the myelin sheath. 345 Jul 86

Single, viable pacemaker cells were isolated from sinoatrial (S-A) and atrioventricular (A-V) nodes by treating with collagenase. In normal Tyrode solution containing 1.8 mM Ca2+, these pacemaker cells had a round configuration and contracted rhythmically at a frequency of about 150-260/min. The amplitude, duration, and maximum rate of rise of the spontaneous action potentials recorded using patch clamp electrodes were similar to those obtained from multicellular preparations. Amplitudes of the recorded membrane current were normalized with reference to the surface area of the cell by assuming the cell shape as a plane oblate spheroid. The membrane resistance of the isolated nodal cells was 14.9 +/- 4.0 k omega . cm2 (n = 12) at about -35 mV and the membrane capacitance was 1.30 +/- 0.24 microF/cm2 (n = 18). The inactivation time course of the slow inward current, isi, was fitted with a sum of two exponentials with time constants of 6.7 +/- 0.6 ms and 46.6 +/- 15.3 ms (n = 4) at +10 mV. The amplitude of isi peaked at 0 approximately +10 mV in the current-voltage relationship and was 18.2 +/- 8.4 microA/cm2. The potassium current, iK, was activated in the voltage range positive to -50 mV and was saturated at about +20 mV. The amplitude of the fully-activated iK at -40 mV was 3.3 +/- 1.4 microA/cm2 (n = 10) and showed an inward-going rectification. The activation of the hyperpolarization-activated current was observed at potentials negative to -70 mV in seven of 14 experiments. The current density and membrane capacitance calculated could be overestimated and the membrane resistance underestimated, because of the presence of caveolae on the cell surface. However, these data give the nearest possible estimates of the electrical constants in the nodal cells, which cannot be measured accurately in the conventional multicellular preparations.
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PMID:Action potential and membrane currents of single pacemaker cells of the rabbit heart. 609 66

1. A study has been made of the ionic currents in voltage-clamped single rabbit nodes of Ranvier at 22-26 degrees C both under normal conditions, and after the nerve fibres had been acutely demyelinated by a variety of treatments designed to lossen the myelin from the axonal membrane. 2. The myelin-loosening treatments included application of various combinations of: lysolecithin (to dissolve the myelin); collagenase (to loosen the connective tissue in the nodal region); high-potassium Locke solution, hypertonic and hypotonic solutions (to induce axonal volume changes). 3. At a critical stage in such treatment (usually after 15-45 min) a large outward current suddenly appeared. 4. There was no substantial change in the size of the measured inward sodium current when measured at this critical stage. 5. The outward current was blocked by internal TEA and caesium ions, had a reversal potential that became more positive when the external potassium concentration was increased, was kinetically similar to the known potassium current in frog fibres, and was therefore assumed to be a potassium current. 6. The phase of large outward current, whenever it appeared, was always accompanied by the appearance of a slow transient capacitative component in the leakage current, which indicated a marked increase in the effective nodal capacity (of 10- to 60-fold). We suggest that the slow transient capacity current reflected charging of newly exposed axonal membrane, probably in the paranodal region, which was uncovered by the various acute demyelination treatments. This internodal membrane seems to contain mostly potassium channels and few, if any, sodium channels. 7. Newly dissected fibres occasionally showed large potassium currents before treatment, particularly if they were deliberately stretched during dissection; a marked slow capacity transient current was consistently present in these fibres. 8. The effects of acute paranodal demyelination on the sodium and potassium currents, and on the transient capacity currents, can be simulated by a model in which the node is coupled to a cable-like paranode which contains Hodgkin--Huxley type potassium channels and which has a much higher leakage resistance. 9. The functional significance of the presence of potassium channels in rhe internodal region (at least in the paranode) of mammalian fibres is discussed.
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PMID:Evidence for the presence of potassium channels in the paranodal region of acutely demyelinated mammalian single nerve fibres. 626 73

Ventricular and atrioventricular nodal cells from guinea pig and rabbit hearts were isolated by perfusing the heart with collagenase (Langendorff perfusion). In these cells the cyclic nucleotides cAMP and cGMP or Ca and EGTA were injected through a microelectrode by pressure (0.5-3 kg/cm2). The effect of injection on both the action potential and the hyperpolarization induced by acetylcholine was studied. The following results were obtained. 1. cAMP prolonged the ventricular action potential and shifted the plateau to more positive potentials. The configuration of the A-V nodal action potential was not detectably changed by cAMP injection, but the spontaneous rate was increased. 2. cGMP first shortened the ventricular action potential. In most experiments this effect was followed by long lasting prolongation of the action potential. 3. Both extracellular and intracellular application of dibutyryl cGMP shortened the ventricular action potential but did not produce a subsequent prolongation. However, prolongation was observed on injection of GMP, the direct metabolite. 4. Injection of cGMP in nodal cells did not hyperpolarize the membrane nor slow the spontaneous rate; rather, an increase in rate was observed. 5. The acetylcholine-induced hyperpolarization was not altered in amplitude or time course by the injection of cAMP, cGMP, Ca or EGTA. 6. The results support the hypothesis that cGMP might be involved in the control of voltage-controlled ionic channels but suggest that it does not play a role as a mediator of the classical muscarinic action i.e. the activation of a specific potassium channel by acetylcholine.
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PMID:The effect of intracellular cyclic nucleotides and calcium on the action potential and acetylcholine response of isolated cardiac cells. 628 Jan 26

Single cells or cell clusters composed of 3-10 cells were isolated from the S-A and A-V nodes of the rabbit heart by coronary perfusion of collagenase dissolved in Ca-free Tyrode solution (0.04%, for 1 hr). For comparison, atrial and ventricular cells were also isolated from the same heart. Shapes of the isolated nodal cell were either rod or round and nodal cells were slightly smaller than ventricular cells. Spontaneous activity was observed in both rod and round nodal cells. The action potentials had the configurations similar to those recorded from larger conventional preparations. The membrane current recorded from the small nodal cell clusters (5-10 cells) by the two-microelectrode voltage clamp technique showed a time course similar to that of previous recordings from conventional preparations, but the amplitude of the currents was 5-10 times smaller. The isolated cells showed normal sensitivities to both acetylcholine and epinephrine. Findings given in this study indicate that the isolated cells maintain the typical membrane characteristics of the nodal cells and that they are suitable for electrophysiological studies of the cardiac pacemaker cell.
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PMID:Spontaneously active cells isolated from the sino-atrial and atrio-ventricular nodes of the rabbit heart. 732 6

Matrix metalloproteinases (MPs) constitute a family of proteolytic enzymes (proteases) that degrade extracellular matrix (ECM) and promote the local or metastatic potential of carcinoma cells, and whose action is restrained by special inhibitors (metalloproteinase inhibitors; MIs). We assessed the role of the MPs stromelysin-3 (STR-3), putative metalloproteinase-1 (PUMP-I), and the gelatinases of molecular weights 72 kDa and 92 kDa, as well as the role of their inhibitors tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2, as markers of metastatic potential in 25 fresh biopsies of squamous-cell lung carcinomas (SCLCs). We examined levels of messenger ribonucleic acid (mRNA) expression for these MPs and inhibitors through Northern blot analysis in 10 carcinomas of high-to-moderate differentiation without lymph-node involvement, and in 15 infiltrative carcinomas of moderate-to-low differentiation with lymph-node involvement. Five cases with significant epithelial atypia and five samples with normal mucosa were used as controls. Expression of STR-3 and TIMP-2 was also assessed immunohistochemically with the avidin-biotin-complex (ABC) technique. We noticed a progressive increase in the expression levels of MPs, especially of STR-3, and of TIMP-2, from the stage of epithelial atypia to the detection of carcinoma, finding the highest values of these substances among carcinomas of low differentiation with nodal metastases. These findings were also confirmed with immunohistochemical analysis. Our results suggest that there is a significant association of the expression of MPs and MIs with both the local and metastatic potential and the degree of cellular differentiation of SCLC, and that this association is clinically important because of its prognostic and therapeutic implications.
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PMID:Association of expression of metalloproteinases and their inhibitors with the metastatic potential of squamous-cell lung carcinomas. A molecular and immunohistochemical study. 941 77

Matrix metalloproteinases (MMPs) are zinc dependent endopeptidases implicated in cancer invasion and metastasis. Gelatin zymography was performed on 84 human breast carcinomas and seven normal breast tissues. The precursor form of MMP-2 (72 kDa) was found in 11 (12%) samples, while its two activated forms, i.e. 62 kDa and 59 kDa, were found in three (6%) and 34 (40%) samples respectively. In contrast to MMP-2, most of the samples (52%) contained MMP-9 in its precursor form. Using ELISA, MMP-1 levels were found in 12% of the samples while MMP-3 levels were found in only 2% of the samples. Levels of MMP-2, -3 and -9 correlated inversely with numbers of nodal metastases. Neither MMP-2 nor -9 levels were significantly related to patient outcome. However, patients with high levels of a 50-kDa gelatinase band after zymography had a significantly better survival than patients with low levels. This species was never observed in normal breast tissue.
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PMID:Assay of matrix metalloproteinases types 1, 2, 3 and 9 in breast cancer. 952 36

Cancer-derived matrix metalloproteinases (MMPs) are proposed to be essential for tumor stromal invasion and subsequent metastasis. To explore the role of MMPs in cancer progression, we examined the expression of various MMPs and tissue inhibitors of MMPs in precancerous and cancerous lesions of the uterine cervix. Immunohistochemical studies demonstrated that MMP-2 and MMP-9 were expressed in >90% of squamous cell carcinomas (SCC) and 83-100% of high-grade squamous intraepithelial lesions (HSIL), but were less frequently expressed in low-grade squamous intraepithelial lesions and normal squamous epithelium (13%). MMP-1, MMP-14, and MMP-15 were detected in 55-81% of SCC cases, and MMP-1 was detected in 39% of HSIL. The tissue inhibitors of MMPs were weakly expressed in SCC (10-61%). By direct analysis of enzyme activities in microdissected specimens, we found that the gelatinolytic activity of MMP-9 was significantly higher in HSIL and SCC than in normal cervix (P < 0.01). The levels of active-form MMP-2 increased progressively from HSIL to SCC of stage I and more advanced stages (P < 0.01). The gelatinolytic activity of MMP-9 and active-form MMP-2 in SCC were strongly correlated with lymphovascular permeation and subsequent lymph node metastasis (P < 0.02). Moreover, the gelatinolytic activity and immunoreactive percentage of both MMP-2 and MMP-9 were significantly higher in SCC cases who had a recurrence than in those who remained free of disease (P < 0.001). Thus, our data demonstrate progressively up-regulated expression of MMP-2 and MMP-9 with SCC progression, and significant associations among their gelatinolytic activity and stage, nodal metastasis, and recurrence.
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PMID:Increased expression and activation of gelatinolytic matrix metalloproteinases is associated with the progression and recurrence of human cervical cancer. 1455 48

Our previously developed approach to the development of QSAR equations for benzene derivatives, originally for phenylalkylamine hallucinogens, has been applied to four new systems: sulfonamide inhibitors of the enzymes carbonic anhydrase, thrombin, trypsin, and Clostridium histolyticum collagenase. The novel features involve the energies and nodal orientations of pi-like orbitals, and an allowance for the symmetry of the benzene nucleus. The resulting equations give better fits, better predictivity and are more easily interpretable than those resulting from traditional QSAR methods.
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PMID:Quantum theoretic QSAR of benzene derivatives: some enzyme inhibitors. 1549 95


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