An alternate mechanism for regulation of leukotriene production in leukocytes: studies with an anti-inflammatory drug, sodium diclofenac
| Autor: | Himanshu V. Kothari, Warren Lee, Edmond C. Ku |
|---|---|
| Rok vydání: | 1987 |
| Předmět: |
Male
Diclofenac Leukotriene B4 Guinea Pigs Leukotriene Production Biophysics Biological Availability Oleic Acids Arachidonic Acids In Vitro Techniques Pharmacology Biochemistry chemistry.chemical_compound Endocrinology Phospholipase A2 Leukocytes medicine Animals Cyclooxygenase Inhibitors Calcimycin Triglycerides Leukotriene Arachidonic Acid Cell-Free System biology Chemistry Rats Inbred Strains Diclofenac Sodium Rats Mechanism of action biology.protein SRS-A Arachidonic acid Cyclooxygenase medicine.symptom Oleic Acid |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 921:502-511 |
| ISSN: | 0005-2760 |
| DOI: | 10.1016/0005-2760(87)90078-6 |
| Popis: | Sodium diclofenac, a potent cyclooxygenase inhibitor, was recently shown to inhibit arachidonic acid conversion to leukotriene products in human leukocytes. This activity was confirmed by radioimmunoassay in calcium ionophore A 23187-stimulated leukocytes isolated from the rat peritoneal cavity and human peripheral blood. Studies with rat peritoneal leukocytes revealed that this effect was not mediated by inhibition of 5-lipoxygenase or phospholipase A2, but rather through modulation of arachidonic acid uptake and release. The potency of this effect was dependent upon cell type; macrophages being more sensitive to the drug than neutrophils. In leukocytes treated with sodium diclofenac, arachidonic acid released from phospholipids in response to A 23187 challenge was reincorporated into triacylglycerols. The drug enhanced the spontaneous uptake of arachidonic acid into the cellular triacylglycerol pool and, in this manner, decreased the availability of intracellular arachidonic acid. Therefore, sodium diclofenac, in addition to inhibition of cyclooxygenase, regulates leukotriene production of inflammatory cells by a mechanism mediated in part through the redistribution of arachidonic acid in lipid pools. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|