Arachidonic Acid Metabolism in the Neonatal Platelet

PEDIATRICS ◽  
1982 ◽  
Vol 69 (6) ◽  
pp. 714-718
Author(s):  
Marie J. Stuart ◽  
Judith B. Allen
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Thromboxane B2 ◽  
Eicosatetraenoic Acid ◽  
Lipoxygenase Product ◽  
Adult Control ◽  
Control Subjects

An assessment of arachidonic acid metabolism in the platelet of the neonate was performed. The uptake of [14C]arachidonic acid into platelets of both the neonate and the adult were similar. Neonatal platelets, however, released a significantly greater amount (P < .001) of prelabeled arachidonic acid (24.7% ± 2.8%) in response to the physiologic agent thrombin when compared with platelets from adult control subjects (14.6% ± 0.8%). When the activities of the lipoxygenase (12-L-hydroxy-5,8,10,14-eicosatetraenoic acid) and cyclooxygenase pathways (12-L-hydroxy-5,8,10-heptadecatrienoic acid and thromboxane B2) were evaluated following incubation of platelets with [14C]arachidonic acid, significant differences were observed between adult and neonatal platelets. Platelets from the neonate produced less (P < .01) thromboxane B2 (11.1% ± 1.7%) when compared with platelets from adult control subjects (19% ± 1.7%). In contrast, the lipoxygenase product 12-L-hydroxy-5,8,l0,14-eicostatetraenoic acid was increased (P < .005) in the platelet from the neonate (41.5% ± 2%), when compared with the adult (31.2% ± 2.1%). The observation that the availability of substrate arachidonic acid is increased in the platelet of the neonate may have general implications in neonatal pathophysiologic processes.

Reduced arachidonate metabolism in ATP-depleted myocardial cells occurs early in cell injury

1990 ◽  
Vol 259 (2) ◽  
pp. H582-H591 ◽  
Author(s):  
G. E. Revtyak ◽  
L. M. Buja ◽  
K. R. Chien ◽  
W. B. Campbell
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Cell Injury ◽  
Arachidonic Acid Metabolism ◽  
Atp Depletion ◽  
Neonatal Rat ◽  
Eicosatetraenoic Acid ◽  
Metabolic Inhibitors ◽  
Early Event ◽  
Myocardial Cells

Exposure of cultured neonatal rat myocardial cells to metabolic inhibitors results in cellular ATP depletion. If prolonged, arachidonic acid is released from membrane phospholipid and irreversible cell injury may ensue. The present study was undertaken to identify the major products of arachidonic acid formed when myocardial cells are depleted of ATP by the metabolic inhibitors 2-deoxy-D-glucose (2-DG) and oligomycin (OG). Under basal conditions, myocardial cells metabolize [3H]arachidonic acid to 6-keto-[3H]prostaglandin (PG)F1 alpha, [3H]PGE2, [3H]PGF2 alpha, 12-[3H]hydroxy-6,8,11,14-eicosatetraenoic acid (12-[3H]HETE) and 11-[3H]HETE, indicating that these cells contain both cyclooxygenase and lipoxygenase pathways. After exposure of myocardial cells to 10 mM 2-DG and 0.1 micrograms/ml OG for 4 h, the basal release of 6-keto-PGF1 alpha and PGE2 is reduced by 3.4-fold and 2-fold, respectively. Supernatants obtained from cells prelabeled with [3H]arachidonic acid and treated with 2-DG and OG for 4 or 12 h did not contain detectable [3H]prostaglandins or [3H]HETEs, but only [3H]arachidonic acid when compared with untreated cells. After 4 and 12 h of treatment with 2-DG and OG, there was a 3.4- and 4.4-fold net release of endogenous arachidonic acid from treated compared with untreated cells. When stimulated with bradykinin, melittin (a phospholipase activator), or arachidonic acid, the synthesis of 6-keto-PGF1 alpha increased to a similar extent in both 2-DG- and OG-treated and -untreated cells. Hence, ATP-depleted myocardial cells do not convert arachidonic acid to oxygenated metabolites under basal conditions. The reduced arachidonic acid metabolism during ATP depletion is not due to direct inactivation of cyclooxygenase or membrane phospholipase. This impairment in arachidonic acid metabolism may represent an early event in myocardial cell injury.

The 15-lipoxygenase product, 8R,15S-diHETE, stereospecifically sensitizes C-fiber mechanoheat nociceptors in hairy skin of rat

1990 ◽  
Vol 63 (5) ◽  
pp. 966-970 ◽  
Author(s):  
D. M. White ◽  
A. I. Basbaum ◽  
E. J. Goetzl ◽  
J. D. Levine
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Thermal Stimulus ◽  
Mechanical Stimuli ◽  
Noxious Heat ◽  
Lipoxygenase Product ◽  
Hairy Skin ◽  
Mechanical Threshold ◽  
C Fiber

1. This study examined the effects of the 15-lipoxygenase product of arachidonic acid metabolism, (8R,15S)-dihydroxyicosa-(5E-9,11,13Z)tetraenoic acid (8R,15S-diHETE), on mechanical thresholds and thermal responses of saphenous nerve cutaneous C-fiber nociceptors that innervate the hairy skin of the rat hindpaw. Single C-fiber mechanoheat nociceptors (C-MH) that had von Frey hair (VFH) thresholds greater than 5 g and were activated by a noxious heat stimulus were chosen for study. We also studied the effects of prostaglandin E2 (PGE2), a cyclooxygenase product of arachidonic acid metabolism, on these nociceptors. 2. The 63 C-MHs studied had a conduction velocity of 0.82 +/- 0.03 m/s (mean +/- SE) and a mechanical threshold of 13.4 +/- 2.4 g. In a subgroup of these (n = 24), the thermal threshold was measured as (44 +/- 1 degree C) (mean +/- SE). 3. 8R,15S-diHETE produced a significant decrease in mechanical threshold of C-MHs (n = 33). The 8R,15S-diHETE-induced sensitization of C-MHs to mechanical stimuli was completely antagonized by coadministration with a stereoisomer, 8S,15S-diHETE (n = 10). 4. The mechanical threshold of C-MHs (n = 10), previously injected with the combination of 8R,15S-diHETE and 8S,15S-diHETE, was significantly reduced by a subsequent injection of PGE2. In a separate group of C-MHs (n = 7), PGE2 was co-injected with 8S,15S-diHETE, which failed to antagonize the sensitizing effect of PGE2 on mechanical threshold. 5. 8R,15S-diHETE also sensitized C-MHs (n = 9) to a thermal stimulus consisting of 37 degrees C for 5 min.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Inhibition of steroid production in Leydig cells by non-steroidal anti-inflammatory and related compounds: evidence for the involvement of lipoxygenase products in steroidogenesis

1984 ◽  
Vol 219 (2) ◽  
pp. 529-537 ◽  
Author(s):  
C J Dix ◽  
A D Habberfield ◽  
M H F Sullivan ◽  
B A Cooke
Keyword(s):  
Arachidonic Acid ◽  
Cyclic Amp ◽  
Leydig Cells ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Eicosatetraenoic Acid ◽  
Dibutyryl Cyclic Amp ◽  
Steroid Production ◽  
Oxygenase Activity ◽  
Dose Dependent

The effect of inhibitors of the cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism on steroidogenesis in rat testis Leydig cells and rat tumour Leydig cells has been investigated. In the presence of nordihydroguaiaretic acid [NDGA; 4,4′-(2,3- dimethylbutan −1,4- diyl)bis[1,2- benzendiol]], 5,8,11,14-eicosatetraynoic acid (ETYA), BW 755C [3-amino-1-[3-(trifluoromethyl)phenyl]-2-pyrazoline hydrochloride] and benoxaprofen [Opren; 2-(2-p-chlorophenyl- benzoxazol −5-yl)propionic acid)] (which inhibit lipoxygenase activity), but not indomethacin and aspirin (which inhibit cyclo-oxygenase activity), a dose-related inhibition of lutropin (LH)-stimulated testosterone and pregnenolone production was obtained (ID50 values of 2.5, 30, 25 and 30 microM for NDGA, ETYA, BW 755C and benoxaprofen were obtained, respectively). BW 755C and benoxaprofen had no significant effect on LH-stimulated cyclic AMP production except at the highest concentrations examined (330 and 380 microM, respectively), whereas NDGA and ETYA inhibited LH-stimulated cyclic AMP production in a dose-dependent manner (ID50 7.0 and 22 microM respectively). However, NDGA and ETYA also caused a dose-dependent inhibition of dibutyryl cyclic AMP-stimulated testosterone and pregnenolone production. The metabolism of exogenous (22R)-hydroxycholesterol or pregnenolone to testosterone by Leydig cells was not inhibited by either NDGA, ETYA or indomethacin. At low concentrations of NDGA and ETYA a significant increase in the conversion of both pregnenolone and (22R)-hydroxycholesterol to testosterone was obtained. Studies in which the metabolism of [14C]arachidonic acid by purified rat tumour Leydig cells was investigated indicate that products are formed by tumour Leydig cells that have similar mobilities in a thin layer chromatography system to 5-L-hydroxy-6,8,11,14-eicosatetraenoic acid, 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid and leukotriene B4. The formation of these products was inhibited to varying degrees by NDGA, BW 755C and benoxaprofen but not by aspirin and indomethacin. These studies demonstrate for the first time that inhibition of lipoxygenase activity but not cyclo-oxygenase activity causes an inhibition of LH- and dibutyryl cyclic AMP-stimulated steroid production and suggest a stimulatory role for products of the lipoxygenase pathway of arachidonic acid metabolism in steroidogenesis. The site of this stimulation is apparently distal to the production of cyclic AMP and before the side chain cleavage of cholesterol.

Regulation of arachidonic acid metabolism in human amnion

1985 ◽  
Vol 110 (1_Suppla) ◽  
pp. S53-S54
Author(s):  
ST. NIESERT ◽  
M. D. MITCHELL ◽  
M. L. CASEY ◽  
P. C. MACDONALD
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Human Amnion

Arachidonic acid metabolism and insulin secretion by isolated human pancreatic islets

Diabetes ◽  
1988 ◽  
Vol 37 (7) ◽  
pp. 992-996 ◽  
Author(s):  
J. Turk ◽  
J. H. Hughes ◽  
R. A. Easom ◽  
B. A. Wolf ◽  
D. W. Scharp ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Human Pancreatic Islets
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