Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urodilatin is a recently discovered natriuretic peptide [ANP-(95-126)] of renal origin, with a primary structure similar to ANP-(99-126). However, urodilatin is not biologically inactivated by renal endopeptidase, and it is a more potent natriuretic agent than ANP-(99-126). The present study was carried out to investigate the renal and systemic effects of urodilatin in rats before and after the induction of congestive heart failure (CHF) by creation of an aortocaval fistula (ACF). Administration of urodilatin in incremental doses (0.75-12 micrograms.kg-1.h-1) to Inactin-anesthetized sham-operated control rats resulted in dose-dependent increases in urine flow, glomerular filtration rate (GFR), excretion of guanosine 3',5'-cyclic monophosphate (cGMP), sodium, and potassium, and a significant decrease in mean arterial blood pressure. In rats with ACF the baseline values for GFR and sodium excretion were significantly lower than in control rats. Urodilatin infusion in rats with ACF led to significant increases in urine flow and sodium excretion, but the absolute levels of diuresis and natriuresis were significantly lower in rats with CHF than in normal rats. When urodilatin was infused into rats with ACF pretreated with neutral endopeptidase inhibitor (NEP-I; SQ-28,063 at a dose of 40 mg/kg iv), the absolute urine flow and sodium excretion were not different from that obtained in control rats. Thus the attenuated natriuretic and diuretic response to ANP-(99-126) in heart failure was not observed with urodilatin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal and systemic effects of urodilatin in rats with high-output heart failure. 153

Application of 10 nM Epidermal Growth Factor (EGF) to single EGFR-T17 fibroblasts induced a marked hyperpolarization that could last for tens of minutes; in many cases the first transient was followed by a series of oscillations of the membrane potential. The outward current responsible for the hyperpolarizing response could be recorded simultaneously to an increase in the intracellular calcium concentration, as measured with the fluorescent indicator fura-2. The conductance was nearly linear in the voltage range from -100 to +50 mV. While the EGF-induced current had many characteristics of a K+ current and was strongly reduced by 50 nM charybdotoxin (ChTx), its reversal potential was apparently more negative than the potassium equilibrium potential (VK). The application of 2 microM ouabain prior to EGF stimulation produced responses that were similar to those obtained without ouabain; however, under these conditions the EGF-induced current showed a reversal potential of -96.6 +/- 3.2 mV, very close to VK. Simultaneous application of both 2 microM ouabain and 50 nM ChTx completely abolished the response. It can be concluded that the response to EGF stimulation in EGFR-T17 cells consists of two components: the first is a current carried through Ca(2+)-activated K+ channels; the second is due to the acceleration of the operation of the Na+/K(+)-ATPase.
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PMID:Two currents activated by epidermal growth factor in EGFR-T17 fibroblasts. 155 Aug 55

Desensitization to the effects of acetylcholine (ACh) or carbachol (CCh) on ACh-regulated potassium current (IK(ACh)) and the voltage-dependent L-type, calcium current (ICa(L)) was studied in single guinea-pig atrial cells under voltage clamp at room temperature (22-24 degrees C). At a holding potential of -40 mV, CCh (100 microM) activated IK(ACh) repeatedly and reproducibly when applied for 15-s periods with 60-s intervals between applications. Prolonged (10 min) exposure to CCh caused a time-dependent decline of IK(ACh) and a marked reduction (desensitization) of the response to subsequent application of CCh. In the absence of guanosine triphosphate (GTP) in the pipette, only partial resensitization occurred within 20 min after CCh washout. The desensitization to CCh could also be obtained when adenosine (20 microM) was used to activate this current. Therefore, this desensitization must be heterologous. In the presence of isoproterenol (ISO, 3 microM), ICa(L) increased. Acetylcholine continued to inhibit this current at a time when its activation of IK(ACh) had become desensitized. Muscarinic inhibition of ICa(L) eventually desensitized but only after IK(ACh) desensitization had occurred. Because of its heterologous nature, as well as of the ability of ACh to desensitize in the presence of intrapipette dextran, which is reported to inhibit beta-adrenergic receptor kinase (beta ARK), it seems unlikely that beta ARK-dependent phosphorylation of the muscarinic receptor (mAChR) accounted for desensitization. The differential desensitization time course is consistent with the hypothesis that different subunits of Gi, the inhibitory guanine nucleotide binding protein, not only transduce the agonist effects of ACh on IK(ACh) and ICa(L) but are also subjected to different inactivation/regulation processes.
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PMID:Muscarinic agonist-induced actions on potassium and calcium channels in atrial myocytes: differential desensitization. 166 56

The topical antiandrogenic activity of potassium canrenoate (CAK), compared with that of spironolactone (SP), was assayed in vivo in female golden Syrian hamsters whose flank organs were stimulated by subcutaneous administration of testosterone propionate. Sebaceous glands and hair were measured by a computerized image analyzer. Pigmented spots, sebaceous gland areas, and the diameter of hairs of the treated flank organs were smaller in the groups that received CAK (1.6 mg/day) and SP (0.4 mg/day). The authors' results showed that CAK may act as a topical antiandrogen on the hamster flank organ when applied in concentrations four times greater than the minimal active dosage of SP. Potassium canrenoate may be a useful weak topical antiandrogen, and it could be used in androgen-related skin disorders involving both sebaceous glands and hair, especially in men. These concentrations could be verified by additional clinical investigations.
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PMID:Topical canrenoic acid. Quantification of the antiandrogenic activity in the hamster flank organ. 175 85

Preservation of the lung is still one of the most challenging problems, because due to limited procurement time not all organs available can be used. The most common procurement technique is flush perfusion of the pulmonary artery system. Alternative methods in clinical use are either the autologous working heart-lung preparation or donor core-cooling (DCC). The own concept presented here, modified to the special demands of multi-organ-procurement, combines DCC and interstitial equilibration adapted to intracellular ion concentration. DCC is induced by extracorporeal circulation (ECC) using a transportable heart lung machine including a highly effective cooling system: cooling circuit based on two parallel heat exchangers with ice-water cooling produced by a high-pressure overflow of a low-temperature ice block (-40 degrees C). While cooling by ECC stepwise hemodilution is achieved by priming volume and incorporation of the cardioplegic solution (Bretschneider-HTK). The aim of equilibration is to lower the extracellular levels of sodium and calcium, and to increase the level of potassium. Additionally, the buffer capacity of donor blood is increased by the incorporated histidine-buffer system (alpha-stat). To avoid donor organ edema the time of ECC should be as short as possible. Using our system donor organ temperatures below 10 degrees C are reached within less than 30 min. In addition to ECC, lung surface cooling is achieved by external overflow with cold arterial blood (internal mammary artery). Besides lung preservation the main advantage of this concept is the profound precooling of all visceral organs before their individual flush perfusion.
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PMID:[The concept of lung and heart-lung preservation within the scope of multiple organ procurement]. 190 76

We describe the cloning and molecular analysis of TRK2, the gene likely to encode the low-affinity K+ transporter in Saccharomyces cerevisiae. TRK2 encodes a protein of 889 amino acids containing 12 putative membrane-spanning domains (M1 through M12), with a large hydrophilic region between M3 and M4. These structural features closely resemble those contained in TRK1, the high-affinity K+ transporter. TRK2 shares 55% amino acid sequence identity with TRK1. The putative membrane-spanning domains of TRK1 and TRK2 share the highest sequence conservation, while the large hydrophilic regions between M3 and M4 exhibit the greatest divergence. The different affinities of TRK1 trk2 delta cells and trk1 delta TRK2 cells for K+ underscore the functional independence of the high- and low-affinity transporters. TRK2 is nonessential in TRK1 or trk1 delta haploid cells. The viability of cells containing null mutations in both TRK1 and TRK2 reveals the existence of an additional, functionally independent potassium transporter(s). Cells deleted for both TRK1 and TRK2 are hypersensitive to low pH; they are severely limited in their ability to take up K+, particularly when faced with a large inward-facing H+ gradient, indicating that the K+ transporter(s) that remains in trk1 delta trk2 delta cells functions differently than those of the TRK class.
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PMID:TRK1 and TRK2 encode structurally related K+ transporters in Saccharomyces cerevisiae. 207 19

In order to evaluate the importance of glycogen for the hepatic tolerance to ischemia, livers of swine fed a glucose-potassium solution for premedication were perfused with either Bretschneider's HTK-solution (histidine-tryptophan-ketoglutarate) or with Euro-Collins-solution (EC) prior to subsequent ischemia at 25 and 5 degrees C. During ischemia, in regular intervals or continuously, energy rich phosphates, lactate, intrahepatic pH and the electrical impedance of liver tissue were determined. The results were compared with corresponding data from swine which had starved for 48 h. Corresponding to the higher glycogen content, energy supply during ischemia was markedly improved by the premedication. Despite high amounts of glucose in the EC-solution, energy supply after glucose-potassium premedication was no better with EC-solution than with HTK-solution. Moreover, glucose uptake led to concomitant cellular water uptake. Electrical impedance measurements during ischemia mirrored improved energetical protection by the glucose-potassium premedication.
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PMID:Glycogen effects on energy state and passive electric properties of liver during protection. 211 13

The purpose of these experiments was to examine the influence of various fluid replacement drinks on exercise-induced disturbances in homeostasis during heavy exercise. Nine trained cyclists performed constant load exercise on a cycle ergometer to fatigue on three occasions with 1-week separating experiments. The work rate was set initially at approximately 85% of VO2max (range 82-88%) with fatigue being defined as a 10% decline in power output below the initial value. During each experiment subjects consumed one of the following three beverages prior to and every 15 min during exercise: (1) non-electrolyte placebo (NEP; 31 mosmol.kg-1); (2) glucose polymer drink containing electrolytes (GP; 7% CHO, 231 mosmol.kg-1), and (3) electrolyte placebo drink without carbohydrate (EP; 48 mosmol.kg-1). Both the GP and EP beverage contained sodium citrate/citric acid (C) as a flavoring agent while C was not contained in the NEP drink. Although seven of nine subjects worked longer during the GP and EP treatment when compared with the NEP trial, the difference was not significant (P greater than 0.05). No differences (P greater than 0.05) existed between the GP and EP treatments in performance time. Exercise changes in rectal temperature, heart rate, delta % plasma volume and plasma concentrations of total protein, free fatty acids, glucose, lactate, potassium, chloride, calcium, and sodium did not differ (P greater than 0.05) between trials.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fluid replacement drinks during high intensity exercise: effects on minimizing exercise-induced disturbances in homeostasis. 231 95

Kidneys were perfused either with Euro-Collins-solution or with HTK-solution of Bretschneider. The perfusion pressure as well as the perfusion flow were measured during a six-minute perfusion. The perfusion resistance was higher in Euro-Collins-kidneys than during HTK-perfusion. The venous outflow of the kidney as well as the ureteral outflow was measured during each minute of the perfusion and has analysed for osmolality, and for sodium and potassium concentrations. In Euro-Collins-kidneys a complete "equilibration" of the extracellular space was not achieved, while during HTK-perfusion concentrations in the venous as in the tubular outflow, similar to those in the HTK-solution itself, could be reached. At the end of the different perfusions, tissue was analysed for biochemical parameters such as ATP, ADP, AMP and lactate as well as for morphological features. Lactate had increased and ATP had decreased during perfusion with Euro-Collins-solution, while ATP had not changed and lactate had decreased during perfusion with HTK-solution. Normal glomerular, tubular and dilated vascular structures can be seen after HTK-perfusion, while a glomerular and vascular contraction takes place during Euro-Collins-perfusion.
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PMID:Short-term perfusion and "equilibration" of canine kidneys with protective solutions. 310 3

We have previously shown that some transformed derivatives of the human osteosarcoma-derived cell line HOS are killed by treatment with 1 microM ouabain at pH 8.2, whereas their nontransformed counterparts are relatively unharmed by the same conditions. HOS cells transformed by v-Ki-ras and RAS, v-fms, or MET are susceptible to 1 microM ouabain while those transformed by v-fes are not. Here we describe the adaptation of this differentially cytotoxic effect as a method to enrich for cells which revert to a nontransformed phenotype. We have optimized parameters which increase the differential cytotoxicity, including pH and potassium concentration during and subsequent to ouabain treatment. The efficiency of this procedure was tested in mixed cell experiments where model populations were constructed consisting of HOS cells mixed with an excess of v-Ki-ras-transformed HOS cells. Two successive OAK treatments (ouabain/alkaline/K+-free) were sufficient to recover nontransformed cells free of ras-transformants as indicated by genetic markers and morphology. This HOS/ouabain system is currently being used to derive revertants of ras-transformed human cells and could facilitate the isolation of genes interacting in the pathways by which these cells are transformed.
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PMID:A system for deriving revertants of oncogene-transformed human cells. 319 49


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