Effects of Free Fatty Acids on Synaptosomal Amino Acid Uptake Systems

Rhoads, Dennis E.; Kaplan, Mustafa; Peterson, N. A.; Raghupathy, E.

doi:10.1111/j.1471-4159.1982.tb07898.x

Cited by 66 publications

(36 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effect of AA is expressed significantly between 30 and 100 ,uM, similar to the concentrations at which AA stimulates glucose transport in 3T3 fibroblasts (22,23) and inhibits glutamate uptake in astrocyte cultures (20 chain appears to be an absolute requirement for the expression ofthe effect, since, as noted earlier, arachidic acid (20:0; i.e., same chain length as AA but no double bond) was without effect, while another unsaturated fatty acid, linolenic acid (18:4), also promoted [3H]2DG uptake. Similar structural requirements have been reported for the effects of long-chain fatty acids on glutamate and 'y-aminobutyric acid uptake inhibition (41) as well as for Na/K-ATPase activity inhibition in the nervous system (42). Results In the cerebral cortex, NE has been shown to stimulate the formation of cAMP followed, among other cAMP-dependent cellular actions, by glycogenolysis (11).…”

Section: Methodsmentioning

confidence: 55%

Arachidonic acid stimulates glucose uptake in cerebral cortical astrocytes.

Martin

Stella

et al. 1993

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

105

View full text Add to dashboard Cite

Arachidonic acid (AA) has recently been shown to influence various cellular functions in the central nervous system. Here we report that AA increases, in a timeand concentration-dependent manner, 2-deoxy-D- [1-3H] uptake, for which the EC50 of NE is 1 IAM. Since the cerebral cortex, the brain region from which astrocytes used in this study were prepared, receives a massive noradrenergic innervation, originating from the locus coeruleus, the effects of NE reported here further stress the notion that certain neurotransmitters may play a role in the regulation of energy metabolism in the cerebral cortex and point at astrocytes as the likely targets of such metabolic effects.Astrocytes play an important role in the maintenance of local homeostasis within the central nervous system (1, 2). In addition to clearing the extracellular space from K+, glutamate, or 'y-aminobutyric acid, whose levels increase as a result of neuronal activity (3)(4)(5), astrocytes may contribute to energy metabolism homeostasis, a function already postulated over a century ago by Golgi (6). For example, astrocytes are the cell type in which glycogen is almost exclusively stored within the central nervous system (7,8), and certain neurotransmitters can readily mobilize this energy reserve (9, 10). Thus, vasoactive intestinal peptide (VIP) and norepinephrine (NE), two neurotransmitters contained in discrete neuronal populations in the cerebral cortex (11), promote, within minutes of application, glycogenolysis in primary cultures of astrocytes (12); within a longer time frame (4-8 hr), these two neurotransmitters promote glycogen resynthesis (13 (29), and elevated extracellular K+ (30). Given the role that astrocytes play in the regulation of energy metabolism in the central nervous system, we set out to determine the consequences of manipulating AA metabolism on glucose uptake in astrocytes. MATERIALS AND METHODS AA was purchased from Nu Chek Prep (Elysian, MN);[3H]2DG (specific activity, 17.3 Ci/mmol; 1 Ci = 37 GBq) and [3H]AA (specific activity, 200 Ci/mmol) were from Amersham. Fetal calf serum (FCS) was purchased from Seromed (Berlin), while Dulbecco's modified Eagle's medium (DMEM) and all other chemicals were from Sigma. AA was dissolved in hexan (1 mg/ml) and stored as a stock solution at -70°C. On the day ofthe experiment, an aliquot was taken, evaporated under a stream of nitrogen, resuspended in 1 ml of diluted [3H]

show abstract

Section: Methodsmentioning

confidence: 55%

Arachidonic acid stimulates glucose uptake in cerebral cortical astrocytes.

Martin

Stella

et al. 1993

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

105

View full text Add to dashboard Cite

show abstract

“…Addition of albumin has also been shown to overcome inhibition of glutamate uptake [142]. Rhoads et al [142[ suggested that during ischaemia, free fatty acids accumulate as the cell membrane is disrupted.…”

Section: Treatment Of Neurotoxicitymentioning

confidence: 99%

Interrelationship between retinal ischaemic damage and turnover and metabolism of putative amino acid neurotransmitters, glutamate and GABA

Robin

Kalloniatis

1992

Doc Ophthalmol

View full text Add to dashboard Cite

Conditions causing a reduction of oxygen availability (anoxia), such as stroke or diabetes, result in drastic changes in ion movements, levels of neurotransmitters and metabolites and subsequent neural death. Currently, there is no clinically available treatment for anoxia induced neural cell death resulting in drastic and permanent central nervous system dysfunction. However, there have been some exciting developments in experimentally induced anoxic conditions where several classes of drugs appear to significantly reduce neural cell death. This report aims to provide the foundations for understanding both the basic mechanisms involved in retinal ischaemic damage and experimental treatments used to prevent such damage. We discuss the normal release, actions and uptake of the fast retinal neurotransmitters, glutamate and GABA, in the vertebrate retina. Immunocytochemistry is used to demonstrate that both glutamate and GABA are found in the macaque retina. Following this is a discussion on how ischaemia may enhance neurotransmitter release or disrupt its uptake, thus causing an increase in extracellular concentration of these neurotransmitters and subsequent neuronal damage. The mechanisms involved in glutamate neurotoxicity are reviewed, because excess glutamate is the likely cause of retinal ischaemic damage. Finally, the mechanisms behind four possible modes of treatment of neurotransmitter toxicity and their advantages and disadvantages are discussed. Hopefully, further research in this area will lead to the development of a rational therapy for retinal, as well as cerebral ischaemia.

show abstract

“…For example, FFA inhibit the Na+-dependent synaptosomal uptake of proline, aspartate, glutamate, and y-aminobutyric acid and reduce synaptosomal Na+,K+-ATPase activity (59). Acyl2Gro stimulate transepithelial sodium transport in frog skin epithelium (60) and markedly increase phospholipase-catalyzed hydrolysis of phospholipid bilayers (61).…”

Section: Discussionmentioning

confidence: 99%

Membrane lipid changes in laminectomized and traumatized cat spinal cord.

Demediuk¹,

Saunders²,

Anderson³

et al. 1985

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

157

105

View full text Add to dashboard Cite

Free fatty acid (FFA), diacyiglycerol (acyl2-Gro), icosanoid, phospholipid, and cholesterol levels were measured in samples of cat spinal cord (L2) that were frozen in situ (i) with vertebrae intact, (ii) at various times after laminectomy, and (iu) at various times after laminectomy with compression trauma to the spinal cord. Tissue samples either were grossly dissected into gray and white portions prior to FFA and acyl2Gro analysis or were used whole for the other lipid types. Gray matter total FFA and acyl2Gro values were abnormally high in samples frozen with vertebrae intact and in those frozen 10 min after laminectomy. This indicates that the surgical procedures resulted in some perturbation of spinal cord lipid metabolism. If the experimental animals were allowed to recover for 90 min after laminectomy, the gray matter FFA and acyl2Gro levels were greatly reduced. Compression of the spinal cord with a 170-g weight for 1, 3, or 5mm (following 90 min of recovery after laminectomy) caused significant elevations of total FFA, acyl2Gro, icosanoids, and phosphatidic acid and significant decreases in ethalamine plasmalogens and cholesterol. Among the total FFA, arachidonic acid was found to have the largest relative increase. Comparisons of gray and white matter demonstrate that, in general, changes in white matter FFA and acyl2Gro were similar to those seen in gray matter. However, the increases in white matter levels of FFA and acyl2Gro were delayed, occurring after the elevations in gray matter. For some FFA (e.g., arachidonate), the rise in white matter occurred as gray matter levels were decreasing. This suggests that the initial alteration in spinal cord lipid metabolism after trauma was in gray matter but, with time, spread radially into white matter.

show abstract

Effects of Free Fatty Acids on Synaptosomal Amino Acid Uptake Systems

Cited by 66 publications

References 18 publications

Arachidonic acid stimulates glucose uptake in cerebral cortical astrocytes.

Arachidonic acid stimulates glucose uptake in cerebral cortical astrocytes.

Interrelationship between retinal ischaemic damage and turnover and metabolism of putative amino acid neurotransmitters, glutamate and GABA

Membrane lipid changes in laminectomized and traumatized cat spinal cord.

Contact Info

Product

Resources

About