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Query: UNIPROT:P06889 (Mol)
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The contribution of the ryanodine-sensitive fraction of canine cardiac sarcoplasmic reticulum to the total issue calcium uptake was estimated by the oxalate-supported calcium uptake rate in canine whole heart homogenates. Ryanodine stimulated this uptake rate nearly three-fold. Ryanodine stimulated this same activity in isolated SR vesicles only two-fold. An analysis of the yield of calcium uptake activity throughout the isolation procedure showed that the largest discrimination between ryanodine-sensitive and ryanodine-insensitive activity occurs at the first centrifugation step. In isolated vesicles, the initial rate of uptake in the absence of oxalate correlated well with the sustained oxalate-support calcium uptake rate, suggesting that oxalate-supported calcium uptake is a good indicator of in vivo SR function. The similarity between the effects of ryanodine on the rate and capacity of calcium uptake in the presence or absence of oxalate is consistent with earlier observations that ryanodine adds effective volume by closing a calcium release channel in a subpopulation of SR. The data also suggest that the ratio of calcium pumping activity to volume in these two populations is not greatly different.
J Mol Cell Cardiol 1988 Dec
PMID:Contribution of the ryanodine-sensitive fraction to capabilities of cardiac SR. 285 53

Normothermic global ischemia of 7, 10, 15 and 60 min was found to depress oxalate supported calcium uptake rate measured either in unfractionated homogenates or isolated sarcoplasmic reticulum. The degree of depression increased with the duration of ischemia. Comparison of the isolated sarcoplasmic reticulum with unfractionated homogenates showed that the isolated sarcoplasmic reticulum was more damaged by ischemia than the unfractionated homogenate. The cause of this discrepancy was not due to inactivation of sarcoplasmic reticulum during isolation but was due to the discard of greater portions of undamaged sarcoplasmic reticulum as the ischemic period increased. Ischemia preferentially affected that sarcoplasmic reticulum most easily fragmented by homogenization. To determine if the depression of sarcoplasmic reticulum function is uniform throughout the isolated fraction, we compared several properties of the isolated fractions. After 10 min of ischemia, extensive properties such as calcium oxalate uptake rate, calcium ATPase rate, calcium oxalate capacity and steady-state calcium loading were depressed 50, 41, 48 and 24% respectively. In contrast, intensive properties such as permeability, calcium-ATPase turnover rate, and ratio of forward nucleotide flux to reverse nucleotide flux were unaffected by ischemia. However, one intensive property, the coupling ratio, was depressed 20%. We conclude from this difference in the effects of ischemia on extensive and intensive properties that the major effect of ischemia is to inactivate the Ca-ATPase.
J Mol Cell Cardiol 1986 Aug
PMID:Effects of ischemia on the isolation and function of canine cardiac sarcoplasmic reticulum. 294 2

The effect of linoleic and arachidonic acid derivatives on ATP-dependent calcium transport was studied in the isolated vesicles from cardiac sarcoplasmic reticulum of guinea-pigs. Oxidation products of linoleic and arachidonic acids, obtained either by autoxidation or incubation with soybean lipoxygenase, effectively blocked in a dose-dependent manner, the net influx of calcium in the absence or presence of 5 mM of oxalate. Unoxidized fatty acids were much weaker at lower concentrations as compared to their oxidized counterparts, except the lipoxygenase-generated product of arachidonic acid which had only a marginal effect even at high concentrations. Autoxidation products of arachidonic acid were the most potent inhibitors of calcium transport. Likewise, autoxidation products of linoleic and arachidonic acids and lipoxygenase-generated products of linoleic acid induced a dose-dependent release of calcium from vesicles previously loaded with 45Ca, and release was further enhanced in the presence of 0.5 mM of EGTA. In contrast, lipoxygenase metabolites of arachidonic acid caused a transient increase in net calcium content. The effect of the fatty acid derivatives on calcium transport did not appear to be due either to the inhibition of Ca2+-ATPase activity or to a non-specific detergent-like action. The effects of oxidized fatty acids, on ATP-dependent calcium accumulation into and release from cardiac microsomal fraction were similar but less potent than those of classical calcium ionophores, X537A or A23187.
J Mol Cell Cardiol 1988 Feb
PMID:The effect of linoleic and arachidonic acid derivatives on calcium transport in vesicles from cardiac sarcoplasmic reticulum. 296 20

Net Ca2+ accumulation in vesicles of dog cardiac sarcoplasmic reticulum (CSR) was evaluated at three different pHs: 6.0, 6.8 and 7.6. The Ca2+ sequestration by CSR depends on Ca2+ concentration and on pH values. The curves that show the relationship between Ca2+ accumulated by CSR and external Ca2+ concentrations were shifted with pH changes, both in the absence and in the presence of potassium oxalate. Considering the curve at pH 6.8 as reference, a lower Ca concentration was needed to obtain the half-maximal value in Ca sequestration under pH 7.6 (0.04 +/- 0.006 and 0.79 +/- 0.09 microM at pH 7.6 and 6.8, respectively). Opposite results were obtained under pH 6.0 (13.66 +/- 1.29 microM). Net calcium release during active accumulation of Ca2+ and Ca2+ efflux from passively 45Ca2+ loaded CSR microsomes were significantly higher at alkaline pH than at acidic pH. The results suggest that in CSR alkaline pH would promote the increase in the rates of both, Ca2+ release and active Ca2+ accumulation, while opposite effects would be expected under acidic pH. Therefore, pH changes may regulate both, the Ca2+ level upon which the SR Ca2+ pump works (permeability effect) and the sequestration rate of the Ca2+ pump (variation in the affinity for calcium).
J Mol Cell Cardiol 1988 Dec
PMID:The effect of pH on the calcium dependence of calcium accumulation in dog cardiac muscle sarcoplasmic reticulum. 297 1

The effect of cAMP-dependent protein kinase on calcium uptake and protein phosphorylation in bovine aortic microsomes was examined. Acid gel electrophoresis demonstrated that the aortic microsomes contained a Ca2+-dependent, hydroxylamine-sensitive phosphoenzyme (Mr 110 kDa), characteristic of the calcium pump in sarcoplasmic reticulum, but showed no evidence of a sarcolemmal calcium pump. Calcium uptake by these aortic vesicles was markedly stimulated by oxalate, whereas calcium uptake by canine cardiac sarcolemmal vesicles was oxalate-independent. Both cAMP plus protein kinase (cAMP-PK) and catalytic subunit of protein kinase stimulated oxalate-supported calcium uptake by bovine aortic microsomes 23 +/- 3% (P less than 0.05) at 0.3 microM Ca2+, but had no effect at 6 to 10 microM Ca2+. Catalytic subunit of protein kinase and cAMP-PK phosphorylated an 11 kDa protein in bovine aortic microsomes which comigrated with canine cardiac phospholamban after boiling in sodium dodecylsulfate. The stoichiometry of the aortic 11 kDa phosphoprotein to 110 kDa phosphoenzyme was approximately 1:1. These data are consistent with the recent identification of phospholamban in various smooth muscles, and suggest that cAMP-mediated vascular relaxation may in part be attributable to stimulation of calcium uptake by the sarcoplasmic reticulum.
J Mol Cell Cardiol 1988 Aug
PMID:Regulation of calcium uptake in bovine aortic sarcoplasmic reticulum by cyclic AMP-dependent protein kinase. 322 9

Methoxyflurane (2,2-dichloro-1,1-difluoro-ethyl methyl ether) is believed to be metabolized via two convergent metabolic pathways. The relative flux through these two metabolic pathways has been investigated using a combination of in vivo surface coil NMR techniques and in vitro analyses of urinary metabolites. Analysis of the measured concentrations of inorganic fluoride, oxalate, and methoxydifluoroacetate in the urine of methoxyflurane-treated rats for 4 days after anesthesia indicates that the anesthetic is metabolized primarily via dechlorination to yield methoxydifluoroacetate. The methoxydifluoroacetate is largely excreted without further metabolism, although a small percentage of this metabolite is broken down to yield fluoride and oxalate, as determined by urine analysis of rats dosed with synthetic methoxydifluoroacetate. At early times after methoxyflurane exposure, the relative concentrations of methoxyflurane metabolites indicate that a significant fraction of the metabolic flux occurs via a different pathway, presumably demethylation, to yield dichloroacetate as an intermediate. Direct analysis of dichloroacetate in the urine using water-suppressed proton NMR indicates that the level of this metabolite is below the detection threshold of the method. Measurements made on the urine of rats dosed directly with dichloroacetate indicate that this compound is quickly metabolized, and dichloroacetate levels in urine are again found to be below the detection threshold. These results demonstrate the quantitative importance of the dechlorination pathway in the metabolism of methoxyflurane in rats.
Mol Pharmacol 1988 May
PMID:In vivo nuclear magnetic resonance studies of hepatic methoxyflurane metabolism. II. A reevaluation of hepatic metabolic pathways. 336 4

Treatment of isolated, working rat hearts with equiactive conditions of buffer containing low Ca2+ (LC), verapamil (Ver), diltiazem (Dil) or nifedipine (Nif) prior to global ischemia (33 min, 37 degrees C) resulted in an equal enhancement in recovery of contractile function, and high energy phosphate (HEP) stores in reperfused hearts. Treatment only during reperfusion did not enhance recovery or HEP stores. Pretreatment with doses which did not depress preischemic contractile function did not afford protection to globally ischemic hearts. In contrast with Dil (2.5 uM), pretreatment with an equiactive concentration of bepridil (Bep) (20 uM) did not preserve contractile function, HEP, or mitochondrial function and did not reduce Ca2+ overload. The Ca2+ was concentrated in mitochondria of hearts receiving no drug or Bep pretreatment (oxalate-pyroantimonate stain). Increasing concentrations of Ver or Dil given before ischemia resulted in a progressive increase in recovery of contractile function which was proportional to depression of preischemic function. The increase in HEP in these hearts was not proportional to drug concentration, preischemic or postischemic function. Pretreatment with Dil reduced lactate production in both normal and K+-arrested ischemic hearts. Energy preservation is only part of the protective mechanisms of Ca2+ antagonists. The Ca2+ antagonists also reduce Ca2+ overload from reperfusion, and may alter Ca2+ compartmentation during ischemia.
J Mol Cell Cardiol 1986 Oct
PMID:Protection of ischemic hearts by Ca2+ antagonists. 349 Dec 15

Various subcellular membrane fractions were isolated from dog aortic smooth muscle by conventional differential centrifugation followed by isopycnic centrifugation on a sucrose density gradient. These subcellular fractions were characterized by membrane marker enzyme activities, morphological features and the electrophoretic patterns on a sodium dodecyl sulfate polyacrylamide gel. Our results showed that the microsomal membrane fraction isolated by differential centrifugation was very heterogeneous and contained substantial amount of plasma membranes which could be further enriched as a light density fraction on the sucrose density gradient. The subcellular distribution of Ca2+ binding in the absence of ATP and Ca2+ transport in the presence of ATP closely paralleled the distribution of plasma membrane markers. The ATP-supported Ca2+ transport was inhibited by several Ca2+ ionophores, enhanced by inorganic phosphate and oxalate ions and cosedimented toward higher density in a continuous source density gradient with plasma membrane marker enzyme activity in the presence of digitonin. Our present work strongly suggests that plasma membrane is the predominant component of microsomal fraction and responsible for most, if not all, of the azide-insensitive ATP-supported Ca2+ accumulation.
J Mol Cell Cardiol 1984 Aug
PMID:Membrane fractionation of canine aortic smooth muscle: subcellular distribution of calcium transport activity. 609 Jun 79

Comparison of Ca2+ uptake by isolated mouse liver mitochondria, and mitochondria prepared from mastocytoma cells grown with and without N6,O2'-dibutyryladenosine 3',5' cyclic monophosphate (DB cyclic AMP) and theophylline showed several differences in their capacity to take up and retain calcium. In particular mitochondria from DB cyclic AMP-treated mastocytoma cells took up more Ca2+ than mitochondria from untreated mastocytoma cells. Ca2+ uptake by mitochondria from DB cyclic AMP-treated cells was also increased in the presence of oxalate whereas oxalate did not affect Ca2+ uptake by mitochondria from untreated mastocytoma cells and it reduced Ca2+ uptake by mouse liver mitochrondria. The results suggest that inhibiting the growth of mastocytoma cells with DB cyclic AMP alters their mitochondrial Ca2+ metabolism.
Mol Cell Biochem 1980 Mar 20
PMID:Changes in motochondrial calcium metabolism after treating mastocytoma cells with N6,O2'-dibutyryladenosine 3',5' cyclic monophosphate. 624 40

The role of the sarcoplasmic reticulum in the regulation of cytosolic calcium is briefly reviewed. A method is described for monitoring calcium efflux from relatively large amounts of SR in a newly designed filtration apparatus using membrane filtration. Two phases of Ca2+ efflux from SR preloaded in the presence of oxalate were observed: an early exponential phase, followed by a phase of constant efflux. Changes in pH from 6.8 to 7.4 resulted in increased efflux. A change in the opposite direction resulted in an initial rapid increase in efflux before the expected decrease occurred. Caffeine (10 and 20 mM) caused increased efflux. Addition of 100 microM EGTA to the buffer resulted in major changes in the exponential phase but not in the phase of constant release, and potentiated the effect of caffeine. The method appears suitable for a variety of pharmacological studies in SR as well as other tissue fractions.
J Mol Cell Cardiol 1984 Feb
PMID:Ca2+ and the sarcoplasmic reticulum. 642 7


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