Role of arachidonic acid metabolites in the action of a beta adrenergic agonist on human monocyte phagocytosis.
The mechanisms by which beta adrenergic stimulation regulates phagocytosis of Candida albicans by human peripheral monocytes (HPM) are characterized. Isoproterenol (ISO) inhibits phagocytosis in a concentration-dependent manner. This effect was blunted by propranolol, inhibitors of phospholipase A2 (PLA2), cyclooxygenase and verapamil, pointing to a participation of arachidonic acid (AA) metabolites and calcium in the phenomenon. Prostaglandin E2 (PGE2) and dibutyryl cyclic AMP (db-cAMP) also exerted the same inhibitory effect on phagocytosis. ISO interacts with beta adrenergic receptors of HPM increasing PGE2 and cAMP. We conclude that the mechanisms by which beta adrenergic stimulation regulates phagocytosis of Candida albicans by HPM appear to be secondary to beta adrenoceptor-mediated hydrolysis of AA accompanied by an increase in PGE2 generation and cAMP production. Both PGE2 and cAMP could act as mediators of the inhibitory action of beta agonists on the HPM-phagocytosis process.
Borda
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ES
Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Cientificas y Técnicas de la República Argentina, Buenos Aires.
Tenenbaum
A
A
Sales
M E
ME
Rumi
L
L
Sterin-Borda
L
L
D000098:Acetophenones / Q000008:administration & dosage / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D003994:Bucladesine / Q000008:administration & dosage / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*; D010120:Oxytocics / Q000008:administration & dosage / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects*; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011433:Propranolol; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology
D000098:Acetophenones; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D010120:Oxytocics; D011943:Receptors, Adrenergic, beta; D016718:Arachidonic Acid; D003994:Bucladesine; D011433:Propranolol; D014700:Verapamil; D000242:Cyclic AMP; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone; D007545:Isoproterenol; C006821:4-bromophenacyl bromide; D002118:Calcium; D007213:Indomethacin