Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rapid, nongenomic effects of testosterone on PRL release in vitro were investigated. Anterior pituitary tissue from adult male rats was stimulated in vitro for 5 or 20 min with testosterone (T; 1 or 100 nM) or testosterone-BSA (T-BSA; 1 or 100 nM) with or without 1.2 mM tannic acid, which enables visualization of secretory granule exocytosis. Within 5 min, both concentrations of T and T-BSA stimulated exocytosis from type 2 lactotrophs (characterized by small spherical granules), but not from type 1 lactotrophs (characterized by large polymorphic granules). The effects of T on type 2 lactotrophs could be blocked by preincubation with dopamine (500 nM), but were not time or concentration dependent, and could not be inhibited by 1) removal of extracellular Ca2+, 2) the L-type Ca2+ channel blocker nifedipine (100 nM), 3) the Ca2+-adenosine triphosphatase inhibitor thapsigargin (150 nM), 4) the PKC inhibitor retinal (10 microM), or 5) the gamma-aminobutyric acidA chloride channel blocker picrotoxin (100 microM). T-BSA (0.1 nM to 1 microM) for 5 or 20 min also caused an increased release of immunoreactive PRL into the medium compared with control incubations. T and T-BSA did not stimulate exocytosis from gonadotrophs or cause LH release. In conclusion, we report for the first time a rapid, nongenomic effect of T on PRL secretion.
 ...
PMID:Nongenomic actions of testosterone on a subset of lactotrophs in the male rat pituitary. 1096 81

Cystic fibrosis (CF) airway epithelia are characterized by enhanced Na(+) absorption probably due to a lack of downregulation of epithelial Na(+) channels by mutant CF transmembrane conductance regulator. Extracellular nucleotides adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP) have been shown to activate alternative Ca(2+)-dependent Cl(-) channels in normal and CF respiratory epithelia. Recent studies suggest additional modulation of Na(+) absorption by extracellular nucleotides. In this study we examined the role of mucosal ATP and UTP in regulating Na(+) transport in native human upper airway tissues from patients with 16 patients with CF and 32 non-CF control subjects. To that end, transepithelial voltage and equivalent short-circuit current (I(SC)) were assessed by means of a perfused micro-Ussing chamber. Mucosal ATP and UTP caused an initial increase in lumen-negative I(SC) that was followed by a sustained decrease of I(sc) in both non-CF and CF tissues. The amiloride-sensitive portion of I(SC) was inhibited significantly in normal and CF tissues in the presence of either ATP or UTP. Both basal Na(+) transport and nucleotide-dependent inhibition of amiloride-sensitive I(SC) were significantly enhanced in CF airways compared with non-CF. Nucleotide-mediated inhibition of Na(+) absorption was attenuated by pretreatment with the Ca(2+)-adenosine triphosphatase inhibitor cyclopiazonic acid but not by inhibition of protein kinase C with bisindolylmaleimide. These data demonstrate sustained inhibition of Na(+) transport in non-CF and CF airways by mucosal ATP and UTP and suggest that this effect is mediated by an increase of intracellular Ca(2+). Because ATP and UTP inhibit Na(+) absorption and stimulate Cl(-) secretion simultaneously, extracellular nucleotides could have a dual therapeutic effect, counteracting the ion transport defect in CF lung disease.
 ...
PMID:Inhibition of amiloride-sensitive epithelial Na(+) absorption by extracellular nucleotides in human normal and cystic fibrosis airways. 1110 28

Phosphorylation of the alpha-subunits of Na(+),K(+)-adenosine triphosphatase in response to insulin, high extracellular glucose concentration, and phorbol 12-myristate 13-acetate was investigated in isolated rat soleus muscle. All three stimuli increased alpha-subunit phosphorylation approximately 3-fold. Phorbol 12-myristate 13-acetate- and high glucose-induced phosphorylation of the alpha-subunit was completely abolished by the PKC inhibitor GF109203X, whereas insulin-stimulated phosphorylation was only partially reduced. Notably, insulin stimulation resulted in phosphorylation of the alpha-subunit on serine, threonine, and tyrosine residues, whereas high extracellular glucose or phorbol 12-myristate 13-acetate stimulation mediated phosphorylation only on serine and threonine residues. Insulin stimulation resulted in translocation of Na(+),K(+)-adenosine triphosphatase alpha(2)-subunit to the plasma membrane and increased Na(+),K(+)-adenosine triphosphatase activity in the same membrane fraction. High glucose had no effect on alpha-subunits distribution. Immunoprecipitation with antiphosphotyrosine antibody and subsequent Western blot analysis with anti-alpha(1)- and -alpha(2)-subunit antibodies revealed that both alpha(1)- and alpha(2)-subunit isoforms underwent phosphorylation on tyrosine residues in response to insulin, although with different time course and magnitude. Thus, we show that insulin-stimulated phosphorylation of Na(+),K(+)-adenosine triphosphatase alpha-subunit occurs via a PKC- and tyrosine kinase-dependent mechanism, whereas high glucose-induced phosphorylation is only PKC-dependent. Phosphorylation of Na(+),K(+)-adenosine triphosphatase alpha-subunits may be involved in regulation of Na(+),K(+)-adenosine triphosphatase activity by insulin or high extracellular glucose in skeletal muscle.
 ...
PMID:Insulin- and glucose-induced phosphorylation of the Na(+),K(+)-adenosine triphosphatase alpha-subunits in rat skeletal muscle. 1145 93

The effect of the phorbol esther phorbol myristate acetate (PMA) on iodide uptake was studied in primary cultures of calf thyroid cells. PMA caused a dose- and time-dependent inhibition of thyrotropin (TSH), forskolin, and db-cAMP stimulation, indicating an effect distal to both TSH receptor and cAMP generation. No action was found on iodide efflux, indicating a selective inhibition of iodide uptake. This inhibition was observed even after 5 minutes of incubation, thus excluding a possible genomic action. Bisindolmaleimide (BS), a specific inhibitor of the protein kinase C (PKC) pathway, reverted the effect of PMA. A similar degree of inhibition of the Na+/K+ adenosine triphosphatase (ATPase) and iodide uptake by PMA was found, thus suggesting a link between both parameters. These results indicate that the PKC pathway inhibits thyroid iodide uptake by an action distal to cAMP generation and probably because of a decrease in Na+/K+-ATPase activity.
 ...
PMID:The protein kinase C pathway inhibits iodide uptake by calf thyroid cells via sodium potassium-adenosine triphosphatase. 1157 49

The renal effects of dopamine are mainly mediated via the dopamine-1 receptor (D1 receptor). This receptor is recruited from intracellular compartments to the plasma membrane by dopamine and atrial natriuretic peptide (ANP), via adenylyl cyclase activation. We have studied whether isoproterenol, a beta-adrenoceptor (beta-AR) agonist that may interact with dopamine in the regulation of rat renal Na+, K+-adenosine triphosphatase (ATPase) activity, can recruit D1 receptors to the plasma membrane. The spatial regulation of D1 receptors was examined using confocal microscopy techniques in LLCPK cells and the functional interaction between dopamine and isoproterenol was examined by studying their effects on Na+, K+-ATPase activity in microdissected single proximal tubular segments from rat. Isoproterenol was found to translocate the D1 receptors from the interior of the cell towards the plasma membrane. The recruitment of dopamine 1 receptors was found to be cyclic adenosine phosphate (cAMP) dependent, while protein kinase C (PKC) activation was not involved. The functional studies on Na+, K+-ATPase activity showed that the effect of isoproterenol was abolished by a D1-like receptor antagonist (SCH 23390), and mediated via protein kinase A (PKA) and PKC dependent pathways. The results provide an explanation for the interaction between G protein-coupled receptors. The effects of isoproterenol on Na+, K+-ATPase activity can be explained by a heterologous recruitment of D1 receptors to the plasma membrane.
 ...
PMID:beta-Adrenoceptor agonist sensitizes the dopamine-1 receptor in renal tubular cells. 1216 72

The hypothesis that protein kinase C (PKC) and tyrosine kinases, as well as serine-threonine and tyrosine phosphatases, are involved in prolactin (PRL) signalling in theca cells harvested from porcine follicles was tested. Theca cells were incubated with PRL for 24 h to stimulate progesterone (P4) production. In addition, treatments included inhibitors of PKC and tyrosine kinases, as well as serine-threonine phosphatase inhibitor and tyrosine phosphatase inhibitor. Prolactin significantly stimulated P4 production by theca cells and all inhibitors suppressed the PRL-stimulated P4 production. After incubation with PRL for 2, 5, 10 or 20 min, theca cells were homogenized and cytosolic and membrane fractions were obtained. This was followed by determination of PKC activity in partially purified subcellular fractions by measuring the transfer of 32P from [gamma-32P] adenosine triphosphatase (ATP) to histone III-S. In unstimulated porcine theca cells the major proportion of PKC activity was present in the cytosol. Incubation of cells with PRL resulted in a rapid, time-dependent increase in the amount of PKC activity in the membrane fraction. Protein kinase C activity in the membrane fraction was maximal after 10 min of cells' exposure to PRL. Protein kinase C activation was assessed also by measuring the specific association of 3H-phorbol dibutyrate (3H-PDBu) with theca cells after treatment with PRL. Prolactin significantly increased 3H-PDBu-specific binding in theca cells. In contrast to PKC, total inositol phosphate accumulation was not affected by PRL in the current study. In summary, PRL stimulated P4 production by porcine theca cells derived from large follicles. The results of the study were consistent with the hypothesis that PKC is one of the intracellular mediators of PRL action in porcine theca cells. Protein kinase C activation does not appear to occur through the action of phosphatidylinositol-dependent phospholipase C. Moreover, the involvement of tyrosine kinases, as well as tyrosine and serine-threonine phosphatases, in PRL signalling in the examined cells is suggested.
 ...
PMID:Prolactin signalling in porcine theca cells: the involvement of protein kinases and phosphatases. 1272 1

GH-releasing peptides (GHRP) are synthetic peptides exerting GH-dependent or GH-independent effects via GH secretagogue receptor on many organs, including the heart. The underlying mechanisms of the cardiotropic properties of GHRP are poorly understood. This study investigates these effects of four GHRP in isolated perfused heart preparations and isolated neonatal and adult ventricular myocytes. The calcium response of cardiocytes to GHRP was visualized using confocal microscopy. All tested GHRP facilitated both ventricular contraction and relaxation in a dose-dependent manner, moderately decreasing coronary flow, but not modifying heart rate. GHRP induced a biphasic increase in intracellular free Ca2+ of the cardiocytes, consisting of a transient phase (phase 1), followed by a plateau phase (phase 2). Phase 1 was abolished by pretreatment with thapsigargin, a Ca2+-adenosine triphosphatase inhibitor of the sarcoplasmic reticulum. The phase 2 response was eliminated by removing extracellular free Ca2+, by verapamil, a voltage-gated Ca2+ channel blocker, or by 24-h pretreatment with phorbol 12-myristate 13-acetate, down-regulating protein kinase C. In isolated (denervated) heart, GHRP have a direct cardiotropic, without chronotropic, effect. GHRP elevate myocardial intracellular free Ca2+ through activating Ca2+ influx via voltage-gated Ca2+ channels and triggering Ca2+ release from thapsigargin-sensitive intracellular Ca2+ stores. Protein kinase C mediates the GHRP-induced Ca2+ influx, but not Ca2+ release. These finding support a number of roles for GHRP in the cardiovascular system.
 ...
PMID:The positive inotropic and calcium-mobilizing effects of growth hormone-releasing peptides on rat heart. 1296 59

It has been documented that angiotensin II (ANG II) (10(-9) M) stimulates proton extrusion via H(+)-adenosine triphosphatase (ATPase) in proximal tubule cells. In the present study, we investigated the signaling pathways involved in the effects of ANG II on H(+)-ATPase activity and on the cytosolic free calcium concentration in immortalized rat proximal tubule cells, a permanent cell line derived from rat proximal tubules. The effects of ANG on pH(i) and [Ca(+2)](i) were assessed by the fluorescent probes, 2',7-bis (2-carboxyethyl)-5(6)-carboxyfluorescein-acetoxy-methyl ester and fluo-4-acetoxy-methyl ester, in the absence of Na(+) to block the Na(+)/H(+) exchanger. In the control situation, the pH recovery rate following intracellular acidification with NH(4)Cl was 0.073+/-0.011 pH units/min (n=12). This recovery was significantly increased with ANG II (10(-9 )M), to 0.12+/-0.015 pH units/min, n=10. This last effect was also followed by a significant increase of Ca(+2) (i), from 99.72+/-1.704 nM (n=21) to 401.23+/-33.91 nM (n=39). The stimulatory effect of ANG II was blocked in the presence of losartan, an angiotensin II subtype 1 (AT(1)) receptor antagonist. H89 [protein kinase A (PKA) inhibitor] plus ANG II had no effect on the pH recovery. Staurosporine [protein kinase C (PKC) inhibitor] impaired the effect of ANG II. Phorbol myristate acetate (PKC activator) mimicked in part the stimulatory effect of ANG II, but reduced Ca(+2) (i). 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (intracellular calcium chelator) alone reduced the pH(i) recovery rate below control levels and impaired the effect of ANG II, in a way similar to that of trimethoxy benzoate (a blocker of Ca(+2) (i) mobilization). We conclude that ANG II regulates rat proximal tubule vacuolar H(+)-ATPase by a PKA-independent mechanism and that PKC and intracellular calcium play a critical role in this regulation.
 ...
PMID:Signaling pathways involved with the stimulatory effect of angiotensin II on vacuolar H+-ATPase in proximal tubule cells. 1668 Apr 84

We assessed the roles of the protein kinase C (PKC) and the tyrosine kinase (TK) signaling pathways in regulating capacitative calcium entry (CCE) in human pulmonary artery smooth muscle cells (PASMCs) and investigated the effects of intravenous anesthetics (midazolam, propofol, thiopental, ketamine, etomidate, morphine, and fentanyl) on CCE in human PASMCs. Fura-2-loaded human PASMCs were placed in a dish (37 degrees C) on an inverted fluorescence microscope. Intracellular Ca2+ concentration ([Ca2+]i) was measured as the 340/380 fluorescence ratio in individual PASMCs. Thapsigargin, a sarcoplasmic reticulum Ca2+-adenosine triphosphatase inhibitor, was used to deplete intracellular Ca2+ stores after removing extracellular Ca2+. CCE was then activated by restoring extracellular Ca2+ (2.2 mM). The effects of PKC activation and inhibition, TK inhibition, and the intravenous anesthetics on CCE were assessed. Thapsigargin caused a transient increase in [Ca2+]i. Restoring extracellular Ca2+ caused a rapid peak increase in [Ca2+]i, followed by a sustained increase in [Ca2+]i; i.e., CCE was stimulated in human PASMCs. PKC activation attenuated (P < 0.05), whereas PKC inhibition potentiated (P < 0.05), both peak and sustained CCE. TK inhibition attenuated (P < 0.05) both peak and sustained CCE. Midazolam, propofol, and thiopental each attenuated (P < 0.05) both peak and sustained CCE, whereas ketamine, etomidate, morphine, and fentanyl had no effect on CCE. Our results suggest that CCE in human PASMCs is influenced by both the TK and PKC signaling pathways. Midazolam, propofol, and thiopental each attenuated CCE, whereas ketamine, etomidate, morphine, and fentanyl had no effect on CCE.
 ...
PMID:Differential effects of intravenous anesthetics on capacitative calcium entry in human pulmonary artery smooth muscle cells. 1834 13

The distal convoluted tubule (DCT) is the shortest segment of the nephron and consists of an early (DCT1) and late part (DCT2). Here, several transport proteins, like the thiazide-sensitive NaCl cotransporter (NCC) and the epithelial magnesium (Mg(2+)) channel (TRPM6), are exclusively expressed. This makes the DCT the major site of active transcellular Mg(2+) reabsorption determining the final excretion in the urine. Following the Mg(2+) influx via the apically localized TRPM6, intracellular Mg(2+) diffuses to the basolateral membrane where it is extruded to the blood compartment via still-unidentified Mg(2+) transporters. Recent years have witnessed multiple breakthroughs in the field of transcellular Mg(2+) reabsorption. Epidermal growth factor and estrogen were identified as magnesiotropic hormones by their effect on TRPM6 activity. Intracellularly, receptor of activated protein kinase C 1 and adenosine triphosphate were shown to inhibit TRPM6 activity through its alpha-kinase domain. Furthermore, dysregulation or malfunction of transcellular Mg(2+) reabsorption in DCT has been associated with renal Mg(2+) wasting. Mutations in TRPM6 are responsible for hypomagnesemia with secondary hypocalcemia. A defect in the gamma-subunit of the Na(+)/K(+)-adenosine triphosphatase causes isolated dominant hypomagnesemia resulting from renal Mg(2+) wasting. Moreover, in Gitelman's syndrome, mutations in NCC also result in impaired transcellular Mg(2+) reabsorption in DCT. This review highlights our recently obtained knowledge concerning the molecular regulation of transcellular Mg(2+) reabsorption.
 ...
PMID:Regulation of magnesium reabsorption in DCT. 1894 82


<< Previous 1 2 3 Next >>