Dexamethasone inhibition of acute opioid physical dependence in vitro is reverted by anti-lipocortin-1 and mimicked by anti-type II extracellular PLA2 antibodies.
Dexamethasone has been shown to inhibit opiate withdrawal, in an in vitro model. In this respect, we suggested that dexamethasone could reduce opiate withdrawal by blocking the release of prostaglandins' precursor, arachidonic acid through protein synthesis dependent-mechanisms (1). Since arachidonic acid is released by the enzyme phospholipase A2 (PLA2) in the present paper we evaluate whether dexamethasone effect may by related to inhibition of PLA2 activity. Therefore, the effect of a neutralizing anti-lipocortin-1 antibody and a polyclonal anti-type II extracellular phospholipase A2 antibody on the opiate withdrawal in vitro was considered. Following a 4 min in vitro exposure to morphine a strong contracture of guinea-pig isolated ileum was observed after the addition of naloxone. Dexamethasone at concentration of 5x10(-5) M reduces of 50% morphine withdrawal and the polyclonal anti-type II extracellular PLA2 antibody (in a dilution 1:1000) mimicked dexamethasone inhibitory effect. Incubation of the ileum preparation with a neutralizing anti-lipocortin-1 antibody (at a dilution of 1:10.000) 30 min before dexamethasone reverted the steroid effects. These results suggest that dexamethasone inhibition of opiate withdrawal is due to extracellular type II PLA2 inhibition through lipocortin-1.
Capasso
A
A
Department of Pharmaceutical Sciences, School of Pharmacy, University of Salerno, Penta, Italy.
Pinto
A
A
Sorrentino
L
L
Cirino
G
G
D000818:Animals; D017305:Annexin A1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D000906:Antibodies / Q000276:immunology*; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D018716:Molecular Mimicry; D009021:Morphine Dependence / Q000188:drug therapy*; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000276:immunology; D054467:Phospholipases A2; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D017305:Annexin A1; D000906:Antibodies; D016718:Arachidonic Acid; D003907:Dexamethasone; D010741:Phospholipases A; D054467:Phospholipases A2