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:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the mode of transepithelial Na+ transport into pancreatic ducts during secretin-dependent NaHCO3 secretion, Na, K-ATPase was first localized within the exocrine pancreas of the pig using a cytochemical reaction for K-dependent p-nitrophenylphosphatase (K-NPPase). K-NPPase staining was confined to the lateral cell membrane bordering the intercellular spaces between ductal cells, negating the possibility of primary active, transcellular Na+ transport into pancreatic ducts. To assess how transepithelial Na+ transport may be coupled to HCO-3 secretion, net flux of Li+ into pancreatic juice was measured following intravenous systemic Li+ loading of 12 secretin infused, anaesthetized pigs. At plasma Li+ 32 (23-35) mmol l-1, Li+ displaced Na+ as accompanying cation to secreted HCO-3, and Li+/Na+ in pancreatic juice matched Li+/Na+ in arterial plasma. During superimposed inhibition of pancreatic water flux by hyperglycaemia, Li+ and Na+ were both transported against a transepithelial concentration gradient. Li+ reduced pancreatic HCO-3 secretion rate by 14 (-2 to -20)%, as well as Na,K-ATPase activity in a separate in vitro assay. The finding that Li+ substituted for Na+ in the secretion even during reduced osmotic water flow suggests that Na+ and Li+ are transported together with secreted HCO-3 into pancreatic juice by an electrogenic mechanism in addition to solvent drag and diffusion.
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PMID:Localization of K-NPPase and Li+ secretion in the exocrine pancreas of the pig. 282 Jan 95

The results of our investigations into the localization of Na+,K+-pump activity in pancreatic and parotid acinar cells and the effects of hormones and neurotransmitters on pump turnover can be integrated with data on other aspects of stimulus-response coupling to construct models of the neurohumoral control of protein, fluid, and electrolyte secretion (Fig. 23). In both tissues, Ca2+ and cyclic AMP serve as intracellular messengers. In pancreatic acinar cells, the Ca2+-dependent pathway activated by the occupation of CCK or cholinergic receptors provides the primary stimulus for digestive enzyme secretion. Cyclic AMP plays a comparatively minor role; VIP and secretin are much less effective stimulators of protein secretion. Conversely, cyclic AMP levels in parotid acinar cells, which are modulated primarily through occupation of beta-adrenergic receptors, are a major determinant of enzyme secretion. Activation of the Ca2+-dependent pathway by cholinergic or alpha-adrenergic agonists or substance P is less important. The presence of dual control processes in each gland suggests that the observed differences in effectiveness of cyclic AMP- versus Ca2+-dependent secretagogues may reflect not different mechanisms, but rather a shift in the relative emphasis placed on each pathway. This emphasis could conceivably result from subtle variations in the interaction between cellular protein kinases and phosphatases and their phosphoprotein substrates. Electrolyte secretion, on the other hand, appears to involve both discrete and common entities. In pancreatic acinar cells from rodent species, cholinergic or CCK receptor occupancy elicits a Ca2+-dependent increase in the open-state probability of nonselective cation channels in the basolateral plasma membrane. The resultant influx of Na+ and efflux of K+ is most probably the factor which activates Na+, K+-pumps. Based on electron probe studies of the effects of cholinergic agonists on acinar cell Na+ and K+ contents discussed earlier, a transient reduction in the intracellular K+/Na+ ratio of up to 4-fold may occur. A shift of this magnitude in the cytoplasmic microenvironment of the Na+, K+-pump clearly would have a stimulatory influence (see discussion by Jorgensen, 1980). In addition, Ca2+ itself may have direct effects on Na+,K+-pump activity. Calcium at levels much above 1 microM progressively inhibits Na+,K+-ATPase activity (Tobin et al., 1973; Yingst and Polasek, 1985). In unstimulated guinea pig pancreatic acinar cells, Ca2+i measured by quin-2 fluorescence was 161 +/- 13 nM (Hootman et al., 1985a) which increased to a maximal concentration of 803 +/- 122 nM following CCh stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuroendocrine control of secretion in pancreatic and parotid gland acini and the role of Na+,K+-ATPase activity. 287 3

To study the mechanism responsible for pancreatic NaHCO3 secretion, the inhibitor NN'-dicyclohexylcarbodiimide (DCCD) was administered to six secretin-infused, anaesthetized pigs. Pancreatic juice was collected from a catheter in the main pancreatic duct. Secretion rate was measured at several arterial pH values in each animal, both before and after DCCD. 15 (14-30) mumol kg-1 body wt DCCD, intra-arterially, reduced pancreatic NaHCO3 secretion from 296 (234-398) to 181 (134-237) mumol min-1 at arterial pH 7.43 (7.42-7.47). Similar fractional reductions of secretion occurred at lower arterial pH. Pancreatic tissue ATP concentration, 1.8 (1.4-2.0) mumol g-1 wet wt, was not changed by DCCD. DCCD, less than or equal to 10(-4) mol l-1, did not change Na,K-ATPase nor carbonic anhydrase activities in separate in vitro assay systems. It is concluded that DCCD reduced pancreatic NaHCO3 secretion by a mechanism not involving ATP depletion nor inhibition of Na,K-ATPase nor carbonic anhydrase activities in pancreatic cells. Because DCCD inhibits proton pumps, DCCD may have reduced NaHCO3 secretion through interfering with a proton pump involved in extruding H+ from HCO-3 secreting cells to interstitial fluid in the pancreas.
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PMID:NN'-dicyclohexylcarbodiimide (DCCD) reduces pancreatic NaHCO3 secretion without changing pancreatic tissue ATP levels. 302 43

To study whether a proton pump is an integral part of the mechanism responsible for secretin-dependent biliary secretion of HCO-3 ions, the proton pump inhibitor N,N'-dicyclohexylcarbodiimide (DCCD) was systemically administered to six anesthetized, secretin-infused pigs. Because biliary HCO-3 secretion varies with arterial pH, secretion rate was measured at several different arterial pH values, before and after DCCD (25 mumol/kg). At arterial pH 7.45, bile flow was 2.1 (1.6-2.9) ml/min, and HCO-3 secretion was 224 (157-311) mumol/min. DCCD reduced bile flow and HCO-3 secretion by 30% and 40%, respectively, independent of arterial pH. In contrast, bile acid secretion, 46 (41-59) mumol/min, was not changed by DCCD. The hepatic adenosine triphosphatase (ATP) level, 2.0 (1.8-2.1) mumol/g wet tissue, was not changed by DCCD. DCCD (10(-4) mol/l) affected neither Na,K-ATPase nor carbonic anhydrase activities in separate in vitro assay systems. The reduction in biliary HCO-3 secretion induced by the proton pump inhibitor DCCD may indicate that a proton pump is integrated into the mechanism responsible for secretin-dependent biliary secretion of HCO-3.
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PMID:DCCD (N,N'-dicyclohexylcarbodiimide) inhibits biliary secretion of HCO-3. 303 16

1. The secretion of sodium, potassium and lithium has been studied in the isolated cat pancreas, perfused with bicarbonate buffered saline solutions of varying composition and osmolality, and stimulated maximally with secretin.2. Under isosmolal conditions, when perfusate sodium chloride was replaced by sucrose, sodium secretion and potassium secretion were directly related to perfusate sodium concentration, [Na](p).3. When osmolality was varied by increasing or decreasing perfusate sodium chloride concentration, the secretion of sodium and of potassium were maximal at [Na](p) of about 120 and 80 mM respectively.4. At a given [Na](p), sodium secretion was greater under hypo-osmolal conditions than under isosmolal conditions.5. When potassium concentration was varied over the range 0-130 mM under isosmolal conditions, by adjusting perfusate NaCl concentration, the secretion of potassium and of sodium were maximal at [K](p) of about 50 and 10 mM respectively. Water flux was maximal at a [K](p) of 10-15 mM. The concentration of potassium in the secretion was almost identical with that in the perfusate over the whole concentration range.6. Replacement of perfusate sodium by lithium reduced the volume of secretion, though a small secretion was maintained even in the complete absence of sodium. The concentration of lithium in the secretion was generally slightly greater than that in the perfusate.7. Omission of potassium from the perfusate reduced secretion by about 65%. Rubidium was a complete substitute for potassium; caesium was not.8. Energy for secretion is derived largely from oxidative phosphorylation. Secretion was reduced by more than 90% under anaerobic conditions and in the presence of dinitrophenol or cyanide. Removal of glucose from the perfusate reduced secretion by more than 50% within 30 min; lactate was a complete substitute for glucose.9. Ouabain, ethacrinic acid and frusimide, known inhibitors of Na(+), K(+)-ATPase activity, all inhibited pancreatic electrolyte secretion.10. The observations are interpreted with reference to the nature of active transport processes involved in pancreatic electrolyte secretion.
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PMID:The secretion of alkali metal ions by the perfused cat pancreas as influenced by the composition and osmolality of the external environment and by inhibitors of metabolism and Na+, K+-ATPase activity. 428 36

Intestinal absorption of amino acids in the chicken occurs by way of processes which are concentrative, Na+-dependent and dependent upon metabolic energy in the form of ATP. Intestinal transport is carrier-mediated, subject to exchange transport (trans-membrane effects) and is inhibitable by sugars, reagents which inactivate sulfhydryl groups, potassium ion, and by deoxpyridoxine, an anti-vitamin B6 agent. It is stimulated by phlorizin, a potent inhibitor of sugar transport, and in Na+-leached tissue by modifiers of tissue cyclic AMP levels, e.g. theophylline, histamine, carbachol and secretin. Separate transport sites with broad, overlapping specificities function in the intestinal absorption of the various classes of common amino acids. A simple model for these sites includes one for leucine and other neutral amino acids, one for proline, beta-alanine and related imino and amino acids, one for basic amino acids, and one for acidic amino acids. Absorption of amino acids appears to be widespread in occurrence in the digestive tract of the domestic fowl; transport has been reported to be present in the crop, gizzard, proventriculus, small intestine and in the colon. By the end of the first week of life post-hatch, the caecum loses its ability to transport. Similarly, the yolk sac loses its ability by the second day post-hatch. Intestinal transport was noted before hatch and was found to be maximal immediately post-hatch. A requirement for Ca2+ appears to be lost after the first week of life post-hatch. The cationic amino acids appear to be reabsorbed by a common mechanism in the kidney. Transport rates of leucine measured in the intestine or in the erythrocyte were found to cluster about discrete values when many individual chickens were surveyed; such patterns may be an expression of gene differences between individuals. Two lines of chickens have been developed, one high and the other low uptake, through selective breeding based on the ability of individual birds to absorb leucine in erythrocytes. High leucine absorbing chickens were found to be more effective in absorbing lysine and glycine, were more effectively stimulated by Na+, had greater erythrocyte Na+, K+-ATPase activity, and their erythrocytes contained about 20% less Na+ than low line erythrocytes. The underlying genetic difference between these lines may reside at the level of the Na+, K+-ATPase and (or) with a regulatory gene determining carrier copies. Amino acid transport in erythrocytes was noted to be highest in pre-hatch chicks and to diminish during post-hatch development.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cell membrane amino acid transport processes in the domestic fowl (Gallus domesticus). 614 42

Repeated administration of troleandomycin increased bile flow but decreased the biliary secretion of bile acids in rats. The increased bile flow was associated with a parallel increase in the biliary clearance of [14C]erythritol. Analysis of the relationship between bile flow and bile acid secretion indicated that, for any given rate of bile acid secretin, bile flow was higher in troleandomycin-treated rats than in control rats. The increased bile flow was associated with an increased activity of Na+,K+-adenosine triphosphatase in liver plasma membranes. The decreased bile acid secretion into bile was associated with a similar decrease in the bile acid pool size, a decreased bile acid synthesis rate and a decreased activity of microsomal cholesterol 7 alpha-hydroxylase. The concentration of bile acids in serum, the hepatic extraction ratio of [3H]taurocholate and its biliary transport maximum were not modified. It is concluded that repeated administration of troleandomycin increases the canalicular bile acid-independent flow but decreases the activity of cholesterol 7 alpha-hydroxylase, the synthesis, the pool size and the biliary secretion rate of bile acid in rats.
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PMID:Effects of troleandomycin administration on cholesterol 7 alpha-hydroxylase activity and bile secretion in rats. 627 Mar 14

Based on studies in the pig, secretin choleresis has been proposed to be initiated by colchicine-inhibitable, exocytic insertion into the basolateral cholangiocyte membrane of intracytoplasmatic vesicles containing a H+ ATPase. Formal proof of this hypothesis in the intact liver of other species, however, is lacking. The effect of the microtubule inhibitor colchicine on the ductular bile formation and HCO3- secretion induced by secretin was, therefore, explored in a secretin-responsive rat model characterized by marked hyperplasia of bile ductules. While colchicine pretreatment significantly decreased basal bile flow from 142.1 +/- 8.8 to 83.4 +/- 8.2 microliters.min-1.kg-1 (p < 0.001) and basal biliary erythritol clearance from 112.7 +/- 6.3 to 69.9 +/- 7.0 microliters.min-1.kg-1 (p < 0.05), it did not significantly affect basal biliary [HCO3-], nor basal biliary bile acid output. Moreover, colchicine did not alter the effects of secretin. Thus, the secretin-induced increments in bile flow, biliary [HCO3-] and biliary HCO3- output averaged 58.2 +/- 13.6 microliters.min-1.kg-1, 16.6 +/- 3.1 mM and 5.3 +/- 1.4 mumol.min-1.kg-1 in vehicle-pretreated controls and 78.4 +/- 12.0 microliters.min-1.kg-1, 16.1 +/- 2.7 mM and 5.1 +/- 0.5 mumol.min-1.kg-1 in colchicine-pretreated animals (all p values = n.s.), respectively. This suggests that, at least in the rat model used, microtubule-dependent mechanisms are involved in basal, bile acid independent canalicular, but not in secretin-induced ductular, bile formation. Inasmuch as microtubule-dependent mechanisms are required for vesicle movement, this argues strongly against an absolute requirement for exocytic vesicle insertion in the ductular choleresis induced by secretin.
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PMID:Colchicine does not inhibit secretin-induced choleresis in rats exhibiting hyperplasia of bile ductules: evidence against a pivotal role of exocytic vesicle insertion. 760 86

The roles of Ca2+ in agonist-induced pepsinogen secretion from guinea pig chief cells remain unclear. We used cholecystokinin octapeptide (CCK-8) or secretin alone or with thapsigargin (TG) to clarify these roles. TG releases Ca2+ from intracellular stores by inhibiting microsomal Ca(2+)-adenosinetriphosphatase (ATPase), thereby depleting intracellular Ca2+ (Cai2+) stores. In most cells TG also causes Ca2+ influx. In the present study, with an extracellular Ca2+ concentration ([Ca2+]o) of 1.5 mM, CCK-8 (0.1 microM) caused a rapid increase in pepsinogen secretion; however, the rate decreased with time. With [Ca2+]o = 0, the initial increase was similar but later secretion was abolished, suggesting that Ca2+ influx was important for sustained secretion. With [Ca2+]o = 1.5 mM, TG (0.1 microM) caused a 2.7-fold sustained increase in in Cai2+ concentration ([Ca2+]i) and a ninefold sustained increase in pepsinogen secretion. With [Ca2+]o = 0, TG caused a transient 66% increase in [Ca2+]i and a 50% increase in pepsinogen secretion. The time course of TG-induced pepsinogen secretion correlated with the time course of TG-induced increases in [Ca2+]i. These data demonstrated that Ca2+ influx itself was a potent stimulant of pepsinogen secretion. We further focused on the roles of increasing [Ca2+]i from Cai2+ stores. With or without extracellular Ca2+ (Cao2+) present, addition of CCK-8 (0.1 microM) 10 min after TG caused no further increase in [Ca2+]i, demonstrating depletion of the inositol 1,4,5-trisphosphate-sensitive pool. The Ca(2+)-mobilizing agent CCK-8 caused no pepsinogen secretion 10 min after TG preincubation, demonstrating that mobilization of Ca2+ from intracellular stores was important in the rapid initial phase stimulation of pepsinogen secretion caused by CCK-8. In contrast, preincubation with TG had no effect on pepsinogen secretion by secretin, an agent that increases adenosine 3',5'-cyclic monophosphate. A 6-min preincubation with TG potentiated the subsequent stimulation of pepsinogen secretion caused by secretin in the presence of Cao2+ where [Ca2+]i remained elevated. However, TG-induced potentiations of secretin-stimulated pepsinogen secretion was abolished once [Ca2+]i had returned to the basal level in the absence of Cao2+.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Thapsigargin defines roles of Ca2+ in initial, sustained, and potentiated stimulation of pepsinogen secretion. 817

Intrahepatic bile duct epithelial cells contribute to bile formation by hormone-dependently secreting HCO3- to bile and H+ to periductular fluid. The present study was undertaken to determine whether the secretin-induced H+ secretion is due to activation of a H(+)-ATPase or Na(+)-H+ exchange. H+ secretion was estimated from the rate of intracellular pH (pHi) recovery after acid loading (24 mM NH4Cl) of microdissected bile ductules from pig liver mounted in a flow-through chamber on the stage of a microscope. pHi was measured from an estimated average of 10-15 epithelial cells using the fluorescent pHi indicator 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein and dual-wavelength excitation of fluorescence. The ducts were superfused with HCO3(-)-free N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffers. We found that secretin induced net H+ secretion of 4.53 +/- 0.7 mumol.ml cell volume-1 x min-1. This H+ secretion was blocked by 10(-6) M bafilomycin A1 but was unaffected by Na+ substitution with choline in the superfusion buffer. The experiments also showed that bafilomycin A1 did not block Na(+)-H+ exchange. The secretin-induced H+ secretion is probably caused by a vacuolar-type H(+)-ATPase and may constitute an important element of the cellular mechanisms causing secretin-dependent ductular HCO3- secretion into bile.
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PMID:Secretin causes H+ secretion from intrahepatic bile ductules by vacuolar-type H(+)-ATPase. 823 55


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