Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

240 Wistar rats were divided into 3 groups to study the postoperative activity of smooth muscle of the anastomosed vessel and the response of it to mechanical and chemical (nor-adrenaline) stimuli, together with the changes of Ca(++)-ATPase following transplantation of the severed limb. The results showed that the post-operative circulatory crisis could set in 3 definite periods with different causes: (1) paralytic period: Within the first 48 hours after operation, no vascular spasm could be provoked anyhow. Should circulatory crisis be found, thrombosis is the most likely cause and prompt surgical exploration with appropriate management is mandatory. (2) Hypersensitive period: 49 to 96 hours after operation, following re-establishment of circulation, the smooth muscle of the vessel, having been recovering in function and in ultrastructure from pathological changes, retains its contractability; while Ca(++)-ATPase, a vascular relaxator, has not yet resumed to be active; the vessel becomes hypersensitive to stimuli of any kind. In case of circulatory crisis, vessel spasm is probably the rule. Conservative management with anti-spasmodic drugs is the treatment of choice. (3) recovery period: 97 to 240 hours after operation, both the anatomical structure and biological activity of the smooth muscle have returned normal and, the Ca(++)-ATPase has also come to play. So that the smooth muscle of vessel resumes its normal function and becomes relatively stable. However, possibility of vascular spasm exists until the tenth post-operative day has passed.
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PMID:[Experimental study of activity of vessels in the smooth muscles and changes in Ca(++)-ATPase following transplantation of severed limb in rats]. 215 Aug

1. The effects of prostaglandins E2 (PGE) and F2alpha (PGF) on membrane potential and isometric tension and cytoplasmic free calcium concentration ([Ca2+]i) and tension were studied in strips of uterine smooth muscle obtained from women undergoing Caesarean delivery at term and during established labour. 2. Prostaglandins (PGs) evoked a biphasic response. The excitatory component consisted of depolarization of the membrane, which initiated spike action potentials, an increase in [Ca2+]i and tension development. The membrane remained depolarized at -19 +/- 1 mV for about 2 min, then repolarized abruptly, [Ca2+]i promptly returned to basal levels, and tension development ceased. 3. This component of the response to PGE or PGF was followed by a slow hyperpolarization which reached -85 +/- 2 mV (n = 22) at term and -70 +/- 2 mV (n = 9) during labour, and during which spontaneous action potentials and tension development did not occur. 4. Nifedipine (10-6 M) abolished spontaneous activity, abolished PG-induced action potentials and reduced the increase in [Ca2+]i (9 +/- 3 %, n = 6), the depolarization (10 +/- 1 mV, n = 14), the tension (2 +/- 1 %, n = 14) and the hyperpolarization (9 +/- 1 mV, n = 14, at term). 5. A variety of K+ channel blockers were without effect on the peak amplitude of the PG-induced hyperpolarization but the latter did not occur in the presence of ouabain (10-6 M) or in K+-free or low-Na+ solutions, suggesting an involvement of the Na+-K+-ATPase pump. 6. In conclusion, a substantial dependence on Ca2+ influx through voltage-operated Ca2+ channels accounts for the importance of membrane potential in regulating contractions in human uterine smooth muscle. The classical excitatory effect of PGE and PGF is followed by hyperpolarization involving the Na+-K+-ATPase pump. The hyperpolarization restricts the response to a single contraction and decreases the frequency of subsequent contractions. The amplitude of the hyperpolarization decreases during labour, allowing contraction frequency to increase. Its persistence at this time ensures complete relaxation between each single robust contraction, preventing spasm of the uterus that would restrict blood flow to the fetus during delivery.
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PMID:Hyperpolarization and slowing of the rate of contraction in human uterus in pregnancy by prostaglandins E2 and f2alpha: involvement of the Na+ pump. 983 29

Increased resistance to blood flow in arteries is built up by blockade of transport of saturated fatty acids of triglycerides in VLDL to cell through apoE/B-100 receptor endocytosis (active transport). This way does not affect the structure of cell membrane. Blockade of the active transport stimulates the compensating activation of lipolysis increasing the level of free saturated fatty acids in the blood. These fatty acids are included into the cell membrane via passive transport. In the membrane fatty acids form local domains with unregulated permeability and nonspecific ion transport: Na+ and Ca2+ enter into cell without any control and K+ and Mg2+ leak out. Responding cells activate Na+, K(+)- and Ca(2+)-ATPase and cholesterol synthesis. Ion pumps activate Na+ and Ca2+ out-fluxes; cholesterol blocks nonspecific ion permeability, but increases membrane microviscosity and inhibits secondary activity of ion pumps, thus forming vicious circle of hypernatriemia and hypercalciemia disturbing functions of loose connective tissue. They increase cell size, promote synthesis and secretion of collagen and elastin. It has led to wail thickening, elasticity drop and artety clear cross section narrowing. The increase of sensitivity to contractility of smooth muscle cells, hyperreactivity towards pressor regulators and resistance to depressor regulators cause artery spasm, peripheral resistance increases and starts up pathogenesis of essential hypertension.
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PMID:[Disruption of saturated fatty acids in cells in the pathogenesis of essential hypertension]. 984 18

Delayed cerebral vasospasm has a major impact on the outcome of subarachnoid hemorrhage. Two important candidates to cause the arterial spasm are the red blood cell product oxyhemoglobin and the vasoconstrictor endothelin-1, although oxyhemoglobin alone is not sufficient to induce cerebral ischemia and endothelin-1 leads to ischemia only at relatively high concentrations. In this study, we demonstrated that the combination of oxyhemoglobin and endothelin-1 triggered spreading neuronal activation in rat cortex in vivo. In contrast with the expected transient increase of regional cerebral blood flow during spreading depression, however, cerebral blood flow decreased profoundly and was long-lasting, paralleled by delayed repolarization of the steady (direct current) potential. These changes are characteristic of cortical spreading ischemia. Replacing oxyhemoglobin for the nitric oxide synthase inhibitor Nomega-nitro-L-arginine mimicked these effects, implicating nitric oxide scavenging functions of oxyhemoglobin. Furthermore, the effect of endothelin-1 was related to a reduction of Na(+)-/K(+)-ATPase activity rather than solely to its vasoconstrictive properties. In conclusion, the threshold concentration of endothelin-1 that induces cerebral ischemia is profoundly reduced via a complex interaction between the neuronal/astroglial network and the cortical microcirculation if nitric oxide availability declines. The results may have implications for the understanding of subarachnoid hemorrhage-related cortical lesions.
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PMID:Ischemia triggered by spreading neuronal activation is induced by endothelin-1 and hemoglobin in the subarachnoid space. 1459 48

Clostridium botulinum, a Gram-positive, anaerobic spore-forming bacteria, is distinguished by its significant clinical applications as well as its potential to be used as bioterror agent. Growing cells secrete botulinum neurotoxin (BoNT), the most poisonous of all known poisons. While BoNT is the causative agent of deadly neuroparalytic botulism, it also serves as a remarkably effective treatment for involuntary muscle disorders such as blepharospasm, strabismus, hemifacial spasm, certain types of spasticity in children, and other ailments. BoNT is also used in cosmetology for the treatment of glabellar lines, and is well-known as the active component of the anti-aging medications Botox and Dysport. In addition, recent reports show that botulinum neurotoxin can be used as a tool for pharmaceutical drug delivery. However, BoNT remains the deadliest of all toxins, and is viewed by biodefense researchers as a possible agent of bioterrorism (BT). Among seven serotypes, C. botulinum type A is responsible for the highest mortality rate in botulism, and thus has the greatest potential to act as biological weapon. Genome sequencing of C. botulinum type A Hall strain (ATCC 3502) is now complete, and has shown the genome size to be 3.89 Mb with a G+C content of approximately 28.2%. The bacterium harbors a 16.3 kb plasmid with a 26.8% G+C content--slightly lower than that of the chromosome. Most of the virulence factors in C. botulinum are chromosomally encoded; bioinformatic analysis of the genome sequence has shown that the plasmid does not harbor toxin genes or genes for related virulence factors. Interestingly, the plasmid does harbor genes essential to replication, including dnaE, which encodes the alpha subunit of DNA polymerase III which has close similarity with its counterpart in C. perfringens strain 13. The plasmid also contains similar genes to those that encode the ABC-type multidrug transport ATPase, and permease. The presence of ABC-type multidrug transport ATPase, and permease suggests putative involvement of efflux pumps in bacteriocin production, modification, and export in C. botulinum. The C. botulinum plasmid additionally harbors genes for LambdaBa04 prophage and site-specific recombinase that are similar to those found in the Ames strain of Bacillus anthracis; these genes and their products may play a role in genomic rearrangement. Completion of genome sequencing for C. botulinum will provide an opportunity to design genomic and proteomic-based systems for detecting different serotypes of C. botulinum strains in the environment. The completed sequence may also facilitate identification of potential virulence factors and drug targets, as well as help characterize neurotoxin-complexing proteins, their polycistronic expression, and phylogenetic relationships between different serotypes.
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PMID:Clostridium botulinum: a bug with beauty and weapon. 1583 1

The small guanosine triphosphatase Rho and its target, Rho kinase, play important roles in both blood pressure regulation and vascular smooth muscle contraction. Rho is activated by agonists of receptors coupled to cell membrane G protein, such as angiotensin II and phenylephrine. Once Rho is activated, it translocates to the cell membrane where it, in turn, activates Rho kinase. Activated Rho kinase phosphorylates myosin light chain phosphatase, which is then inhibited. This sequence stimulates vascular smooth muscle contraction, stress fiber formation,and cell migration. In this way, Rho and Rho kinase activation have important effects on several cardiovascular diseases. Currently available substances that specifically inhibit this signaling pathway could offer clinical benefits in several cardiovascular, as well as noncardiovascular diseases, such as arterial hypertension, pulmonary hypertension, cerebral or coronary spasm, post-angioplasty restenosis, and erectile dysfunction.
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PMID:[Rho/Rho kinase signal transduction pathway in cardiovascular disease and cardiovascular remodeling]. 1605 29

Intracellular Ca2+ is critical for regulating airway smooth muscle (ASM) tension. A rapid rise in the intracellular Ca2+ concentration ([Ca2+]i) of ASM cells is crucial for modulating the intensity and length of the ASM contraction. Because this rapid increase in [Ca2+]i largely depends on the balance between Ca2+ released from intracellular Ca2+ stores and extracellular Ca2+ entry, exploring the mechanisms mediating Ca2+ transport is critical for understanding ASM contractility and the pathogenesis of bronchial contraction disorders. Transient receptor potential vanilloid 4 (TRPV4) is a highly Ca2+-permeable non-selective cation channel that mediates Ca2+ influx to increase [Ca2+]i, which then directly or indirectly regulates the contraction and relaxation of ASM. The [Ca2+]i returns to basal levels through several uptake and extrusion pumps, such as the sarco(endo)plasmic reticulum Ca2+ ATPase and inositol 1,4,5-trisphosphate receptors (IP3Rs), the plasmalemmal Ca2+ ATPase, and the plasma membrane Na+/Ca2+ exchanger (NCX). Thus, to further understand ASM tension regulation in normal and diseased tissue, the present study examined whether an interaction exists among TRPV4, IP3Rs, and NCX. The TRPV4-specific and potent agonist GSK1016790A increased [Ca2+]i in mouse ASM cells, an effect that was completely blocked by the TRPV4-specific antagonist HC067047. However, GSK1016790A induced relaxation in mouse tracheal rings precontracted with carbachol in vitro. To determine the mechanism underlying this TRPV4-induced relaxation of ASM, we blocked specific downstream molecules. We found that the GSK1016790A-induced relaxation was abolished by the NCX inhibitors KB-R7943 and LiCl but not by specific inhibitors of the Ca2+-activated large-, intermediate-, or small-conductance K+ channels (BKCa, IK, and SK3, respectively). The results of co-immunoprecipitation (co-IP) assays showed an interaction of TRPV4 and IP3R1 with NCXs. Taken together, these findings support a physical and functional interaction of TRPV4 and IP3R1 with NCXs as a novel TRPV4-mediated Ca2+ signaling mechanism and suggest a potential target for regulation of ASM tension and treatment of respiratory diseases, especially tracheal spasm.
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PMID:TRPV4 Complexes With the Na+/Ca2+ Exchanger and IP3 Receptor 1 to Regulate Local Intracellular Calcium and Tracheal Tension in Mice. 3186 74