New evidence for the role of cyclic AMP in the release of mitochondrial calcium

Juzu, H. A.; Holdsworth, E. S.

doi:10.1007/bf01869125

Cited by 14 publications

(4 citation statements)

References 9 publications

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“…Although cyclic AMP has been suggested to release Ca 2+ from mitochondria (Juzu & Holdsworth, 1980), mitochondrial inhibitors failed to impair the hyperpolarizing responses to cyclic AMP-mediated secretagogues in Intestine 407 cells. Ca 2+ ions mobilized upon stimulation with VIP and secretin appear to originate from the microsomal store since the prior treatment with caffeine preferentially abolished VIP-and secretin-induced hyperpolarizing responses (Fig.…”

Section: Discussionmentioning

confidence: 87%

Intestinal secretagogues increase cytosolic free Ca2+ concentration and K+ conductance in a human intestinal epithelial cell line

et al. 1989

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A human intestinal epithelial cell line (Intestine 407) is known to retain receptors for intestinal secretagogues such as acetylcholine (ACh), histamine, serotonin (5-HT) and vasoactive intestinal peptide (VIP). The cells were also found to possess separate receptors for secretin and ATP, the stimulation of which elicited transient hyperpolarizations coupled to decreased membrane resistances. These responses were reversed in polarity at the K+ equilibrium potential. The hyperpolarizing responses to six agonists were reversibly inhibited by quinine or quinidine. By means of Ca2(+)-selective microelectrodes, increases in the cytosolic free Ca2+ concentration were observed in response to individual secretagogues. The time course of Ca2+ responses coincided with that of hyperpolarizing responses. The responses to ACh and 5-HT were abolished by a reduction in the extracellular Ca2+ concentration down to pCa 7 or by application of Co2+. Thus, in Intestine 407 cells, not only the intestinal secretagogues, which are believed to act via increased cytosolic Ca2+ (ACh, 5-HT and histamine), but also those which elevate cyclic AMP (VIP, secretin and ATP) induce increases in cytosolic Ca2+, thereby activating the K+ conductance. It is likely that the origin of increased cytosolic Ca2+ is mainly extracellular for ACh- and 5-HT-induced responses, whereas histamine, VIP, secretin and ATP mobilize Ca2+ from the internal compartment.

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Section: Discussionmentioning

confidence: 87%

Intestinal secretagogues increase cytosolic free Ca2+ concentration and K+ conductance in a human intestinal epithelial cell line

et al. 1989

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“…On the other hand, hepatocytes held in calcium-free medium for 0 or 6 hr after calcium depletion showed contrasting effects of glucagon on AIB transport even though glucagon enhanced the production of cAMP at both the times (Table 1). Glucagon enhanced AIB transport when added 0 hr after calcium depletion but not when added 6 (1), and in isolated hepatocytes, in which both glucagon and dibutyryl cAMP increased calcium efflux (26), and by the release of calcium from isolated liver mitochondria by cAMP (27).…”

Section: Discussionmentioning

confidence: 94%

Calcium-dependent hormonal regulation of amino acid transport and cyclic AMP accumulation in rat hepatocyte monolayer cultures.

Kelley¹,

Evanson²,

Potter³

1980

Proc. Natl. Acad. Sci. U.S.A.

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The effect of glucagon, epinephrine, norepinephrine, dexamethasone, insulin, and. dexamethasone plus glucagon on the transport of 2-aminoisobutyric acid (AIB) and that of glucagon on the production of cyclic AMP were examined in rat hepatocyte monolayer cultures under three different culture conditions involving calcium. The hepatocytes were studied in calcium-containing medium after treatment with or without 0.033% dimethyl sulfoxide, the solvent for the calcium ionophore A23187 (calcium controls) calcium-free medium after treatment with A23187 (calciumdepleted); and calcium-containing medium after treatment with ionophore (calcium-restored). The basal and hormonally regulated rates of AIB transport for hepatocytes in calcium control and calcium-depleted cultures were comparable. The restoration of calcium in calcium-restored cultures increased the basal and the hormonally stimulated transport of AIB when compared to the other conditions. Calcium markedly enhanced the stimulation of AIB transport in cultures treated with glucagon, catecholamines, and Nexamethasone plus glucagon. The level of cyclic AMP production in response to glucagon in calcium control and calcium-depleted cultures was the same and it was conspicuously higher than the level in calcium-restored cultures. Varying the concentration of calcium in the medium used to maintain the hepatocytes in calcium control cultures did not affect the stimulation of AIB transport or cyclic AMP production by glucagon. However, in calcium-restored cultures, increasing the calcium concentration of the medium resulted in increased stimulation of AIB transport and decreased production of cyclic AMP by glucagon. In the calcium-restored cultures, calcium in the absence of glucagon enhanced AIB transport but had no effect on cyclic AMP production. Cultures maintained for 6 hr in calcium-free medium after the depletion of calcium showed a 6-to 7-fold increase in the production of cyclic AMP in response to glucagon, but no stimulation of AIB transport. We suggest that mobilization of cellular calcium by glucagon either directly or through cyclic AMP mediates its stimulation of amino acid transport.Calcium regulates a variety of cellular functions, including the hormonal regulation of gluconeogenesis (1-3). Amino acids are substrates for hepatic gluconeogenesis and their availability, particularly during fasting, could limit the rate of gluconeogenesis. Although several hormones have been shown to regulate the transport of amino acids in perfused liver (4-6), liver slices (7), or isolated hepatocytes (8-18), the mechanisms for the hormonal regulation of amino acid transport are poorly understood. The present studies were undertaken to examine the hormonal regulation (by glucagon, epinephrine, norepinephrine, dexamethasone, and insulin) of amino acid transport in hepatocyte monolayers under three different culture conditions involving cellular calcium. Because it has been suggested that glucagon effects result from alterations in the level of intracellular cyclic A...

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“…Since isolated mitochondria can rapidly take up large quantities of calcium from the suspension medium (reviewed by Lehninger, Carafoli & Rossi, 1967), the question of the cellular mechanisms which control 0022-2631/81/0062-0053 $02.20 9 1981 Springer-Verlag New York Inc. the release of this accumulated calcium has also concerned many investigators (reviewed by Bygrave, 1978;Nicholls & Brand, 1980;and Lehninger, Vercesi & Bababunmi, 1978;Harris, A1-Shaikhaly & Baum, 1979;L6tscher, Winterhalter, Carafoli & Richter, 1979;Roman, Gmaj, Nowicka &Angielski, 1979;Haworth, Hunter & Berkoff, 1980;Juzu & Holdsworth, 1980). However, most experiments designed to investigate this question have tested the ability of a given agent to induce a release of calcium from isolated mitochondria which have previously been permitted to accumulate relatively large amounts (greater than 20 nmol/mg protein) of the cation (Borle, 1974;Peng, Price, Bhuvaneswaran & Wadkins, 1974;Binet & Volfin, 1975;Schotland & Mela, 1977 ;Lehninger et al, 1978 ;Harris et al, 1979;L6tscher et al, 1979;Roman et al, 1979).…”

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confidence: 99%

Evidence for two compartments of exchangeable calcium in isolated rat liver mitochondria obtained using a45Ca exchange technique in the presence of magnesium, phosphate, and ATP at 37°C

Barritt

1981

J. Membrain Biol.

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The distribution of calcium between isolated rat liver mitochondria and the extramitochondrial medium at 37 degrees C and in the presence of 2 mM inorganic phosphate, 3 mM ATP, 0.05 or 1.1 mM free magnesium and a calcium buffer, nitrilotriacetic acid, was investigated using a 45Ca exchange technique. The amounts of 40Ca in the mitochondria and medium were allowed to reach equilibrium before initiation of the measurement of 45Ca exchange. At 0.05 mM free magnesium and initial extramitochondrial free calcium concentrations of between 0.15 and 0.5 microM, the mitochondria accumulated calcium until the extramitochondrial free calcium concentration was reduced to 0.15 microM. Control experiments showed that the mitochondria were stable under the incubation conditions employed. The 45Ca exchange data were found to be consistent with a system in which two compartments of exchangeable calcium are associated with the mitochondria. Changes in the concentration of inorganic phosphate did not significantly affect the 45Ca exchange curves, whereas an increase in the concentration of free magnesium inhibited exchange. The maximum rate of calcium outflow from the mitochondria was estimated to be 1.7 nmol/min per mg of protein, and the value of K0.5 for intramitochondrial exchangeable calcium to be about 1.6 nmol per mg of protein. Ruthenium Red decreased the fractional transfer rate for calcium inflow to the mitochondria while nupercaine affected principally the fractional transfer rates for the transfer of calcium between the two mitochondrial compartments. The use of the incubation conditions and 45Ca exchange technique described in this report for studies of the effects of agents which may alter mitochondrial calcium uptake or release (e.g., the pre-treatment of cells with hormones) is briefly discussed.

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New evidence for the role of cyclic AMP in the release of mitochondrial calcium

Cited by 14 publications

References 9 publications

Intestinal secretagogues increase cytosolic free Ca2+ concentration and K+ conductance in a human intestinal epithelial cell line

Intestinal secretagogues increase cytosolic free Ca2+ concentration and K+ conductance in a human intestinal epithelial cell line

Calcium-dependent hormonal regulation of amino acid transport and cyclic AMP accumulation in rat hepatocyte monolayer cultures.

Evidence for two compartments of exchangeable calcium in isolated rat liver mitochondria obtained using a45Ca exchange technique in the presence of magnesium, phosphate, and ATP at 37°C

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