Levorphanol inhibition of Ca++ binding to synaptic membranes in vitro

Levorphanol inhibits Ca ++ binding to synaptic membranes in a dose dependent fashion (0.5–10nM) and induces release of calcium previously bound to membranes. The inhibition is noncompetitive and exhibits a K i of 9 × 10 −9 M. Naloxone (10 nM) blocks this inhibition while dextrophan (100nM) is without effects. The Ca ++ binding exhibits a high affinity (K D =0.84 μ M) and a saturable capacity of 350 picomles/mg protein. The binding curve is sigmoid with a Hill coefficient of 2.2, while in the presence of levorphanol (0.5 to 50nM), the curve becomes hyperbolic with a Hill coefficient of 1.1. The data suggest the calcium and opiate receptor binding sites are in close proximity and may be functionally linked through sub-unit interactions.