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)

The mechanisms for Ca++ release from caffeine-sensitive stores were investigated in freshly dispersed porcine myometrial cells utilizing the fura-2 method. Because the caffeine-sensitive Ca++ store has not been detected in myometrium of mammals, we first determined the existence of this type of store in porcine myometrial cells. The evidence includes: 1) caffeine (1-33 mM)-induced concentration-dependent increase in the intracellular Ca++ concentration ([Ca++]i) in both the presence and absence of extracellular Ca++ and 2) although ryanodine alone (< or = 10 microM) failed to change [Ca++]i, it inhibited the response to caffeine in a use-, concentration- and time-dependent manner. In the cell suspension study, the amount of Ca++ released by 10 mM caffeine was found to be inversely proportional to the amount released by preadministration of caffeine (1-33 mM). In the single cell study, about 30% of cells responded to only a certain concentration of caffeine and the others responded to caffeine gradually. Thapsigargin, an inhibitor of Ca(++)-adenosine triphosphatase in sarcoplasmic reticulum, failed to increase [Ca++]i. Pretreatment with thapsigargin inhibited the response to caffeine in a time- and concentration-dependent manner. These results suggest that in porcine myometrial cells: 1) the Ca++ released from the caffeine- and ryanodine-sensitive store is in an all-or-none manner through compartments of stores or the entire store of a cell and 2) the release process is regulated by luminal Ca++ content of the stores.
 ...
PMID:The caffeine- and ryanodine-sensitive Ca++ store in porcine myometrial cells: its heterogeneity of all-or-none Ca++ release. 853 Oct 66

The cellular mechanisms by which mechanical forces regulate myocardial function such as secretion of atrial natriuretic peptide (ANP), are uncertain. We studied the effects of thapsigargin, a specific inhibitor of sarcoplasmic reticulum Ca2+ adenosine triphosphatase, that depletes intracellular Ca2+ stores, on basal and atrial stretch-induced ANP secretion in the isolated, perfused, paced rat heart preparation. Addition of 300 nM thapsigargin into the perfusate caused gradual increase in perfusion pressure, contractile force and ANP release (P < 0.001). Thapsigargin pretreatment at concentrations (30 and 100 nM) that did not affect baseline cardiac function or hormone secretion blocked mechanical stretch-induced increase in ANP secretion. These results suggest that thapsigargin-sensitive intracellular Ca2+ pools serve as mechanotransducers in the mechanical loading-induced changes in cardiac myocytes.
 ...
PMID:Stretch-induced increase in atrial natriuretic peptide secretion is blocked by thapsigargin. 885 2

This study evaluates the role of internal calcium store depletion in the activation of ionic fluxes and steroidogenesis in adult rat Leydig cells. Thapsigargin and cyclopiazonic acid, two inhibitors of Ca(2+)-adenosine triphosphatase of internal Ca(2+) stores induced a dose-dependent rise in intracellular Ca(2+) concentrations following kinetics that would not be expected if the calcium rise was dependent only on internal calcium store depletion, but it was in keeping with the presence of calcium influx from the external medium. In fact, chelation of external calcium with EGTA during the plateau phase reduced the intracellular calcium concentration to basal levels. When added in calcium-free medium, thapsigargin and cyclopiazonic acid still induced a rise in the intracellular calcium concentration that was transient, and when calcium was added back to the medium, a rapid and sustained intracellular calcium increase was observed. Thapsigargin and cyclopiazonic acid induced a dose-dependent rise in testosterone secretion in the presence and absence of calcium in the external medium, although in calcium-free medium this stimulatory effect was lower. Leydig cell plasma membrane potential monitoring demonstrated that thapsigargin and cyclopiazonic acid induced first a rapid hyperpolarization, followed by a sustained depolarization phase that was reversed by the addition of the calcium-chelating agent EGTA. In the absence of calcium in the external medium the first phase of hyperpolarization was still present, but it was not followed by plasma membrane depolarization but by the slow return of plasma membrane potential to resting levels. The readdition of calcium to the external medium induced the rapid plasma membrane depolarization. Plasma membrane hyperpolarization was completely abolished by Leydig cell preincubation with the K(+) channel blockers tetraethylammonium and charybdotoxin. Leydig cell preincubation with K(+) channel inhibitors reduced the thapsigargin-stimulated Ca(2+) influx from the external medium and testosterone secretion. These results suggest that internal Ca(2+) stores depletion in rat Leydig cells induces a rise in intracellular Ca(2+), determining important plasma membrane potential variations that influence testosterone secretion.
 ...
PMID:Store-operated calcium influx and stimulation of steroidogenesis in rat Leydig cells: role of Ca(2+)-activated K(+) channels. 1151 64

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

Alcohol consumption has long been associated with cell damage, and it is thought that it is involved in approximately 40% of cases of acute pancreatitis. In the present study, we have investigated the early effects of acute ethanol exposure on cholecystokinin octapeptide (CCK-8)-evoked calcium (Ca2+) signals in mouse pancreatic acinar cells. Cells were loaded with fura-2 and the changes in fluorescence were monitorized using a spectrofluorimeter. Our results show that stimulation of cells with 1 nM CCK-8 led to a transient increase in [Ca2+]c, which consisted of an initial increase followed by a decrease of [Ca2+]c toward a value close to the prestimulation level. In the presence of 50mM ethanol, CCK-8 lead to a greater Ca2+ mobilization compared to that obtained with CCK-8 alone. The peak of CCK-8-evoked Ca2+ response, the "steady-state level" reached 5 min after stimulation, the rate of decay of [Ca2+]c toward basal values and the total Ca2+ mobilization were significantly affected by ethanol pretreatment. Thapsigargin (Tps) induced an increase in [Ca2+]c due to its release from intracellular stores. After stimulation of cells with CCK-8 or Tps in the presence of 50mM ethanol, a greater [Ca2+]c peak response, a slower rate of decay of [Ca2+]c, and higher values of [Ca2+]c were observed. The effects of ethanol might result from a delayed or reduced Ca2+ extrusion from the cytosol toward the extracellular space by plasma membrane Ca2+ adenosine triphosphatase (ATPase), or into the cytosolic stores by the sarcoendoplasmic reticulum Ca2+-ATPase. Participation of mitochondria in Ca2+ handling is also demonstrated. The actions of ethanol on CCK-8 stimulation of cells create a situation potentially leading to Ca2+ overload, which is a common pathological precursor that mediates pancreatitis.
 ...
PMID:Ethanol impairs calcium homeostasis following CCK-8 stimulation in mouse pancreatic acinar cells. 1877 72