Acetylcholine stimulates hydrolysis of 32P-labeled phosphatidic acid in guinea pig synaptosomes

Schacht, Jochen; Agranoff, Bernard W.

doi:10.1016/0006-291x(73)91335-1

Cited by 44 publications

(11 citation statements)

References 19 publications

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“…The data of Wells and Wells (5) (18)(19)(20). By using methods which allow a more direct measurement of Ptdlns concentration, we were able to show a definite loss of the phospholipid in response to AcCho, strongly suggesting stimulation of the enzyme PtdIns-Ins phosphohydrolase by the neurotransmitter.…”

Section: Discussionmentioning

confidence: 81%

Myoinositol and phosphatidylinositol metabolism in synaptosomes from galactose-fed rats.

Warfield¹,

Segal²

1978

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

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The effects of experimental galactose toxicity on inositol and phosphatidylinositol (PtdIns) metabolism in synaptosomes from 0-to 30day-old rats were investigated. Galactose toxicity was induced by feeding mothers a 40% galactose diet from the 12th day of pregnancy until 19 days postpartum when the offspring were weaned onto the maternal diet. There was no decrease in myoinositol concentrations and only a small decrease in PtdIns in synaptosomes from galactose-fed rats relative to glucose-fed controls. Synaptosomes from rats on the two diets converted equivalent amounts of [ U-14Clglucose to inositol and PtdIns. Acetylcholine stimulated [2-MlHinositol incorporation into PtdIns while producing a net decrease in Ptdlns concentration in synaptosomes from 22-to 30-day-old rats. However, the phospholipid response to acetylcholine in synaptosomes from galactose-fed rats was impaired. Thus, the acetylcholine-stimulated labeling of PtdIns was 40-50% lower in these synaptosomes while the effect on Ptdlns concentration was reduced by a maximum of 55%. The data suggest that galactose-fed rats may have either a deficiency in the number of acetylcholine receptors or a defect in some step between receptor-neurotransmitter interaction and PtdIns breakdown.Since mental retardation appears to be the only incompletely reversible outcome of galactosemia caused by deficiency of the enzyme, galactose-1-phosphate uridylyltransferase, much interest has centered around the cause of the neurotoxicity. Wells and coworkers (1, 2) have reported increased concentrations of galactose and galactitol and a decrease in the concentration of free and lipid-bound myoinositol (Ins) in brain and nerve tissue of several galactosemic infants, and Schwarz (3) has demonstrated an increased concentration of galactose-1-phosphate in the nervous system of such patients. However, the mechanism by which galactose or its metabolites exert their toxic effects on the developing nervous system remains to be elucidated.In rats and chickens, experimental galactose toxicity results in decreased brain development, decreased nerve conduction, and decreased concentrations of glucose and of free amino acids in brain and nerve tissues (4). Wells and Wells (5) reported elevation of galactitol concentration and depression of free and lipid-bound Ins concentrations in brains of developing rats whose mothers were maintained on high galactose diets throughout pregnancy and lactation. In addition, these investigators demonstrated a decrease in the ability of brain slices from young galactose-toxic rats to convert [14C]glucose to Ins or phosphatidylinositol (PtdIns). Kozak and Wells (6) demonstrated decreased labeling of phosphatidic acid (PtdA) and PtdIns in brains of galactose-toxic chickens after intracranial injection of 32P1, although no change in total amount of phospholipid phosphorus was observed.These observations suggesting an impairment in Ins and Ins phospholipid synthesis or metabolism in galactose-toxic animals are of special significance in view of the e...

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Section: Discussionmentioning

confidence: 81%

Myoinositol and phosphatidylinositol metabolism in synaptosomes from galactose-fed rats.

Warfield¹,

Segal²

1978

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

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“…We have found that phosphatldic acid phosphohydrolase actlvity [phosphatldate phosphohydrolase (EC. 3.1.3.9)) (PAPase), a key enzyme I n the regulation of phosphollpld blosynthesls (8, 17). begins to increase I n fetal rabblt lung on day 26 of gestatlon and Its actlvlty contlnues to increase and reaches adult levels Just prior to parruritlon (18).…”

Section: Introduction Discussionmentioning

confidence: 99%

Fetal Lung Maturation IV: The Release of Phosphatidic Acid Phosphohydrolase and Phospholipids into the Human Amniotic Fluid

Jiménez

Johnston

1976

Pediatr Res

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ExtractThe relationship between surface active material and phosphatidic acid phosphohydrolase (PAPase) activity was examined in human amniotic fluid after centrifugation a t 105,000 x g for one hour. The distibution of PAPase activity between the pellet and supernatant fractions was similar to that of phospholipids in the amniotic fluid. The majority of the PAPase activity was found to be associated with the pellet fraction. Similarly, 82% of the phospholipid was also present in this fraction. Of the total palmitate present in the original sample, approximately 90' 70 was found in the pellet after centrifugation. Palmitic acid constituted 75% of all fatty acids present in the phosphatidylcholine identified in the pellet. By sharp contrast only 4% of the total protein was pelletized by centrifugation. The pelletized fraction isolated from amniotic fluid after 105,000 x g centrifugation closely resembles the lamellar bodies in: (1) its phospholipid pattern; ( 2 ) palmitate concentration in phosphatidylcholine; and, (3) the presence of PAPase activity with a high specific activity. Collectively, these findings lend strong support to the concept that a lamellarlike body is released from fetal lung into the amniotic fluid. Speculation

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“…These data suggest that PAPase may play a central role in phospholipid metabolism. In sup port of this concept is the observation that the activity of this enzyme in liver can be modulated by dietary changes [23] and the brain shows an increase in PAPase activity following the addition of acetyl-choline [20].…”

Section: Discussionmentioning

confidence: 99%

“…The enzyme phos phatidic acid phosphatase or phosphohydrolase (PAPase; EC 3.1.3.4) catalyzes the hydrolytic cleavage of phosphatidic acid forming the pro ducts sn 1,2-diglycerides and orthophosphate. Evidence suggesting the im portance of this enzyme in the control of glyceride and phospholipid bio synthesis in liver and brain tissue has been reported [11,20]. Phospho-hydrolase-kinase-coupled enzyme systems in many cases function as con trol points in metabolism as a consequence of their close relationship to the phosphorylation potential of the cell.…”

mentioning

confidence: 99%

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Fetal Lung Maturation

Schultz¹,

Jiménez²,

MacDonald³

et al. 1974

Gynecol Obstet Invest

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The specific activity of phosphatidic acid phosphohydrolase (PAPase) has been determined in the fetal rabbit lung, from day 20 of gestation to 2 days post partum. The activity increases four fold from day 23 to adult levels on day 30. No change was found in the liver phosphatidic acid phosphohydrolase or lung CDP-choline:diglyceride transferase activities. The increase in activity of the enzyme in fetal rabbit lung precedes by 24 h, the increase in phosphatidylcholine concentration. The increase in phosphatidic acid phosphohydrolase activity may function in the regulation of phosphatidylcholine biosynthesis in the developing lung by increasing the availability of substrates for phosphatidylcholine biosynthesis.

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Acetylcholine stimulates hydrolysis of 32P-labeled phosphatidic acid in guinea pig synaptosomes

Cited by 44 publications

References 19 publications

Myoinositol and phosphatidylinositol metabolism in synaptosomes from galactose-fed rats.

Myoinositol and phosphatidylinositol metabolism in synaptosomes from galactose-fed rats.

Fetal Lung Maturation IV: The Release of Phosphatidic Acid Phosphohydrolase and Phospholipids into the Human Amniotic Fluid

Fetal Lung Maturation

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