DEXAMETHASONE INHIBITION OF ACUTE OPIOID PHYSICAL-DEPENDENCE IN-VITROIS REVERTED BY ANTI-LIPOCORTIN-1 AND MIMICKED BY ANTI-TYPE-II EXTRACELLULAR PLA(2) ANTIBODIES

Dexamethasone has been shown to inhibit opiate withdrawal, in an in vi tro model. In this respect, we suggested that dexamethasone could redu ce opiate withdrawal by blocking the release of prostaglandins(1) prec ursor, arachidonic acid through protein synthesis dependent-mechanisms (1). Since arachidonic acid is released by the enzyme phospholipase A (2), (PLA(2)) in the present paper we evaluate whether dexamethasone e ffect may by related to inhibition of PLA(2) activity. Therefore, the effect of a neutralizing anti-lipocortin-1 antibody and a polyclonal a nti-type II extracellular phospholipase A(2) antibody on the opiate wi thdrawal in vitro was considered. Following a 4 min in vitro exposure to morphine a strong contracture of guinea-pig isolated ileum was obse rved after the addition of naloxone. Dexamethasone at concentration of 5x10(5) M reduces of 50% morphine withdrawal and the polyclonal anti- type II extracellular PLA(2), 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 r esults suggest that dexamethasone inhibition of opiate withdrawal is d ue to extracellular type II PLA(2) inhibition through lipocortin-1. (C ) 1997 Elsevier Science Inc.