Inhibitory mechanism of opioid binding to receptor by phospholipase A2.

1. The inhibition of [3H]naloxone binding to the opioid receptor upon short-term incubation with phospholipase A2 (Plase A2) was abolished by treatment with BSA, but not after long-term incubation. 2. In contrast to the restorative effect of BSA on the strong inhibition occurring with Plase A2, BSA only partially abolished the inhibitory effect of arachidonic acid or lysophosphatides, even though the degree of inhibition was slight. 3. These results suggest that Plase A2 products only become associated with hydrophobic receptor sites or with phospholipids near to the receptor, thus reversibly inhibiting opioid binding, and that irreversible inhibition occurs through release of the phospholipid necessary for receptor binding.