Characterization of the hormone-sensitive Ca2+ uptake activity of the hepatic endoplasmic reticulum

Andia-Waltenbaugh, Ana Maria; Lam, Arky; Hummel, Larry; Friedmann, Naomi

doi:10.1016/0304-4165(80)90418-3

Cited by 38 publications

(14 citation statements)

References 43 publications

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“…This confirms the observations made in other laboratories that no effects on either IP3 or its parent phospholipid are apparent after 30 s or 1 min of glucagon (> 10 nM) treatment (Creba et al, 1983;Charest et al, 1985;Poggioli et al, 1986). Paradoxically it has been reported that glucagon treatment leads to a stimulation of Ca2+ uptake into a liver microsomal preparation by a cyclic AMP-dependent mechanism, and this would appear to work against a glucagon-induced release from this store (Taylor et al, 1979(Taylor et al, , 1980Andia-Waltenbaugh et al, 1980). During work in our laboratory on the effects of hormone treatment of rats on liver mitochondrial metabolism (for reviews see Halestrap, 1981Halestrap, , 1986Halestrap et al, 1983Halestrap et al, , 1985 we began to investigate possible changes in phospholipid composition of the mitochondrial membrane induced by hormones (Quinlan et al, 1983;Halestrap et al, 1983;Armston & Halestrap, 1984).…”

Section: Introductionsupporting

confidence: 84%

Effects of glucagon and Ca2+ on the metabolism of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in isolated rat hepatocytes and plasma membranes

Whipps¹,

Armston²,

Pryor³

et al. 1987

Biochemical Journal

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Rat hepatocytes whose phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) had been labelled for 60 min with 32P were treated with glucagon for 10 min or phenylephrine for 2 min. Glucagon caused a 20% increase in PIP but no change in PIP2 whereas phenylephrine caused a similar increase in PIP but a 15% decrease in PIP2. Addition of both hormones together for 10 min produced a 40% increase in PIP. A crude liver mitochondrial fraction incubated with [32P]Pi and ADP incorporated label into PIP, PIP2 and phosphatidic acid. The PIP2 was shown to be in contaminating plasma membranes and PIP in both lysosomal and plasma-membrane contamination. A minor but definitely mitochondrial phospholipid, more polar than PIP2, was shown to be labelled with 32P both in vitro and in hepatocytes. The rate of 32P incorporation into PIP was faster in mitochondrial/plasma-membrane preparations from rats treated with glucagon or if 3 microM-Ca2+ and Ruthenium Red were present in the incubation buffer. Loss of 32P from membranes labelled in vitro was shown to be accompanied by formation of inositol 1,4,5-trisphosphate (IP3) and inositol 1,4-bisphosphate, and was faster in preparations from glucagon-treated rats or in the presence of 3 microM-Ca2+. It is concluded that glucagon stimulates both PIP2 phosphodiesterase and phosphatidylinositol kinase activities, as does the presence of 3 microM-Ca2+. The resulting formation of IP3 may be responsible for the observed release of intracellular Ca2+ stores. The roles of a guanine nucleotide regulatory protein and phosphorylation in mediating these effects are discussed.

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Section: Introductionsupporting

confidence: 84%

Effects of glucagon and Ca2+ on the metabolism of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in isolated rat hepatocytes and plasma membranes

Whipps¹,

Armston²,

Pryor³

et al. 1987

Biochemical Journal

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“…This enhancement by glucagon of the maximal rate of mitochondrial Ca 2+ uptake without changing K0. 5 of the reaction is similar to the hormone's effect on microsomal Ca 2+ uptake kinetics, which we have recently reported (69). Other compounds which enhance mitochondrial calcium uptake such as phosphate ion (70), adenine nucleotides (33), and phenethylbiguanide (68), also enhance Vmax without affecting K0.…”

Section: -supporting

confidence: 57%

The effect of glucagon on the kinetics of hepatic mitochondrial calcium uptake

1981

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Previous work by this and other laboratories has shown that glucagon administration stimulates calcium uptake by subsequently isolated hepatic mitochondria. This stimulation of hepatic mitochondrial Ca2+ uptake by in vivo administration of glucagon was further characterized in the present report. Maximal stimulation of mitochondrial Ca2+ accumulation was achieved between 6-10 min after the intravenous injection of glucagon into intact rats. Under control conditions, Ca2+ uptake was inhibited by the presence of Mg2+ in the incubation medium. Glucagon treatment, however, appeared to obliterate the observed inhibition by Mg2+ of mitochondrial Ca2+ uptake. Kinetic experiments revealed the usual sigmoidicity associated with initial velocity curves for mitochondrial calcium uptake. Glucagon treatment did not alter this sigmoidal relationship. Glucagon treatment significantly increased the V max for Ca2+ uptake from 292 +/- 22 to 377 +/- 34 nmoles Ca2+/min per mg protein (n = 8) but did not affect the K 0.5, (6.5-8.6 microM). Since the major kinetic change in mitochondrial Ca2+ uptake evoked by glucagon is an increase in V max, the enhancement mechanism is likely to be an increase either in the number of active transport sites available to Ca2+ or in the rate of Ca2+ carrier movement across the mitochondrial membranes.

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“…It was found that microsomes (microsomal fraction), together with mitochondria to act as a high-capacity backing pump, behaved in a manner comparable with that of hepatocytes made permeable to Ca2+ by digitonin treatment (Becker et al, 1980). Both mitochondria and microsomes from rat liver have been shown to alter their Ca2+-pumping activity in a stable way in response to various hormone treatments (Hughes & Barritt, 1978;Taylor et al, 1979Taylor et al, , 1980Friedmann & Johnson, 1980;Andia-Waltenbaugh et al, 1980;Reinhart & Bygrave, 1981). However, hormonally sensitive Ca2+ transport has been localized in the 'heavy' microsomal fraction rather than in the 'light' fraction (Taylor et al, 1979).…”

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confidence: 99%

“…However, hormonally sensitive Ca2+ transport has been localized in the 'heavy' microsomal fraction rather than in the 'light' fraction (Taylor et al, 1979). Previous studies on the kinetic properties of the Ca2+-uptake system of microsomes (Moore et al, 1975;Bygrave, 1978;Andia-Waltenbaugh et al, 1980) have concentrated on the fraction sedimenting between 125OOg for 20min and 105 OOOg for 60min (Moore et al, 1975). The 'heavy' microsomal fraction isolated by the method of Reinhart & Bygrave (1981), sedimenting between 7700g for 10min and 35000g for 20min, has not been investigated in the same way.…”

mentioning

confidence: 99%

Kinetic properties of the Ca2+-accumulation system of a rat liver microsomal fraction

Dawson¹

1982

Biochemical Journal

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1. By using Ca-EGTA buffers, the Km for Ca2+ uptake into rat liver heavy microsomes (microsomal fraction) was found to be 0.2 microM free Ca2+. 2. In the absence of oxalate, these vesicles accumulate about 20 nmol of Ca2+/mg of protein. Efflux of Ca2+ from the vesicles is much faster at pH 7.6 than at pH 6.8, but does not apparently show saturation kinetics or any stringent requirement for external ions. 3. The steady-state distribution of Ca2+ between the microsomes and the medium in the presence of ATP and the absence of oxalate is dependent on Ca2+ load. When the vesicles are loaded to 50% capacity, the external free Ca2+ concentration is 70 nM. 4. The affinity of heavy microsomes for Ca2+ is such that is seems likely that they has a dominant role in the determination of cytoplasmic free Ca2+ concentrations.

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Characterization of the hormone-sensitive Ca2+ uptake activity of the hepatic endoplasmic reticulum

Cited by 38 publications

References 43 publications

Effects of glucagon and Ca2+ on the metabolism of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in isolated rat hepatocytes and plasma membranes

Effects of glucagon and Ca2+ on the metabolism of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in isolated rat hepatocytes and plasma membranes

The effect of glucagon on the kinetics of hepatic mitochondrial calcium uptake

Kinetic properties of the Ca2+-accumulation system of a rat liver microsomal fraction

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