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)

Leukotriene B4 decreases the mechanical and thermal thresholds of C-fiber nociceptors in the hairy skin of the rat

1988 ◽  
Vol 60 (2) ◽  
pp. 438-445 ◽  
Author(s):  
H. A. Martin ◽  
A. I. Basbaum ◽  
E. J. Goetzl ◽  
J. D. Levine
Keyword(s):  
Acetic Acid ◽  
Glacial Acetic Acid ◽  
Leukotriene B4 ◽  
Thermal Stimulation ◽  
Mechanical Stimuli ◽  
Noxious Heat ◽  
C Fibers ◽  
Mechanical Threshold ◽  
C Fiber ◽  
Heat Threshold

1. We have recently shown that leukotriene B4 (LTB4), a product of the 5-lipoxygenase pathway of arachidonic acid metabolism, sensitizes nociceptors to mechanical stimuli. The present study examined whether LTB4 also induces a heat sensitization of cutaneous C-fiber nociceptors. The C-fiber nociceptors studied had von Frey hair thresholds greater than 5 g and were characterized according to their responses to noxious heat and chemical stimuli, including glacial acetic acid, bradykinin, and capsaicin. Thirty-four of the C-fibers that were activated by intense thermal stimulation were also activated by topical application of glacial acetic acid. They were classified as C-polymodal nociceptors (2, 28). Those that were activated by intense mechanical and thermal stimulation, but were unresponsive to acid, were classified as C-mechanoheat nociceptors (27). 2. Ninety-four percent of C-polymodal nociceptors and 60% of C-mechanoheat nociceptors were sensitized by LTB4. All C-fiber nociceptors that showed a decrease of their heat threshold also had a decrease of their mechanical threshold. LTB4 (75 ng) lowered the average heat threshold from 45 degrees C to 35 degrees C and produced an average decrease in the mechanical threshold of 86%. 3. The magnitude of the LTB4-evoked decrease in thermal threshold was similar to that produced by 75 ng of prostaglandin E2 (PGE2). These data demonstrate that LTB4 sensitizes C-mechanoheat nociceptors to both mechanical and thermal stimuli. 4. We conclude that LTB4 may contribute to the component of hyperalgesia that is resistant to nonsteroidal anti-inflammatory agents.

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.

Regulation of cutaneous C-fiber heat nociceptors by nerve growth factor in the developing rat

1994 ◽  
Vol 71 (3) ◽  
pp. 941-949 ◽  
Author(s):  
G. R. Lewin ◽  
L. M. Mendell
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Sural Nerve ◽  
Mechanical Stimuli ◽  
Noxious Heat ◽  
Nerve Growth ◽  
C Fibers ◽  
Mechanical Threshold ◽  
C Fiber ◽  
Developing Rat

1. Previous work has indicated that nerve growth factor (NGF) is an important factor for the development of nociceptive A-delta fibers. Here we asked if the availability of NGF during the first 2 wk of development can influence the phenotypic development of unmyelinated afferent C-fibers. 2. To do this, we treated newborn rats with antibodies to NGF from postnatal day (PND) 2-14, a treatment known not to lead to cell death, or with exogenous NGF (PND 0-14). Untreated litter mates served as controls. When the animals were mature (5-20 wk later), they were anesthetized (urethan, 1.25 g/kg ip) and single-unit recordings were made from sural nerve C-fibers in dorsal root filaments. To obtain an unbiased estimate of the physiological types present, an electrocutaneous search technique was employed to isolate the location of the putative receptive field of the C-fiber being studied within the sural nerve territory. This technique enabled us to acquire a sample of C-fibers that was unbiased by natural search stimuli which are often damaging to skin. 3. We found that the proportion of C-fibers that could be driven by noxious heat and mechanical stimuli (C-mechanoheat fibers, C-MH) was reduced from 28% (11/40 fibers) of the sample in controls to 10% (3/31 fibers) in anti-NGF treated animals. The C-MH fibers appeared to have been replaced by a novel type of pressure receptor with an unusually low mechanical threshold (mean 0.86 +/- 0.58 compared with 13.0 +/- 8.3 g for control mechanonociceptors).(ABSTRACT TRUNCATED AT 250 WORDS)

Sensitization of group III muscle afferents to static contraction by arachidonic acid

1990 ◽  
Vol 68 (3) ◽  
pp. 861-867 ◽  
Author(s):  
D. M. Rotto ◽  
H. D. Schultz ◽  
J. C. Longhurst ◽  
M. P. Kaufman
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Pressor Response ◽  
Receptive Fields ◽  
Muscle Afferents ◽  
Arachidonic Acid Metabolism ◽  
Mechanical Stimuli ◽  
Group Iii ◽  
Static Contraction ◽  
Lipoxygenase Products

The afferent arm of the reflex are responsible for the pressor response to static contraction is comprised of group III and IV fibers. The nature of the contraction-induced stimulus activating these fibers remains unclear. Evidence suggests that most group III afferents are sensitive to mechanical stimuli, whereas most group IV afferents are sensitive to metabolic stimuli. Recently, in anesthetized cats, stimulation of group III mechanoreceptors has been shown to have a role in the reflex pressor response to static contraction. In skin, the sensitivity of thin fiber mechanoreceptors to distortion of their receptive fields has been shown to be increased by both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism. Therefore, in barbiturate-anesthetized cats we recorded the responses of group III muscle afferents to static contraction before and after arachidonic acid (1-2 mg ia) and/or indomethacin (5 mg/kg iv). Arachidonic acid increased the responses of group III afferents (n = 11) to contraction by 265% (from 0.17 +/- 0.07 to 0.62 +/- 0.24 impulses/s; P less than 0.025). Indomethacin decreased the responses of group III afferents (n = 9) to contraction by 61% (from 1.00 +/- 0.37 to 0.39 +/- 0.16 impulses/s; P less than 0.025). Arachidonic acid given after indomethacin increased the responses of two of four group III afferents to contraction. We conclude that both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism sensitize group III muscle afferents to static contraction.

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

The interaction Between Arachidonic Acid Metabolism and Homocysteine

2020 ◽  
Vol 20 ◽  
Author(s):  
Elisa Domi ◽  
Malvina Hoxha ◽  
Bianka Hoxha ◽  
Bruno Zappacosta
Keyword(s):  
Cardiovascular Disease ◽  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Neurological Diseases ◽  
Arachidonic Acid Metabolism ◽  
Epoxyeicosatrienoic Acids ◽  
Pathological Conditions ◽  
Literature Searches ◽  
Hydroxyeicosatetraenoic Acids ◽  
Improve Health

Purpose: Hyperhomocysteinemia (HHcy) has been considered a risk factor for different diseases including cardiovascular disease (CVD), inflammation, neurological diseases, cancer and many other pathological conditions. Likewise, arachidonic acid (AA) metabolism is implicated in both vascular homeostasis and inflammation as shown by the development of CVD following the imbalance of its metabolites. Aim of The Review: This review summarizes how homocysteine (Hcy) can influence the metabolism of AA. Methods: In silico literature searches were performed on PubMed and Scopus as main sources. Results: Several studies have shown that altered levels of Hcy, through AA release and metabolism, can influence the synthesis and the activity of prostaglandins (PGs), prostacyclin (PGI₂), thromboxane (TXA), epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs). Conclusions: We believe that by targeting Hcy in AA pathways, novel compounds with better pharmacological and pharmacodynamics benefits may be obtained and that this information is valuable for dietician to manipulate diets to improve health.

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