Morphine tolerance-induced modulation of [3H]glyburide binding to mouse brain and spinal cord

Modulation by opioids of ATP-gated potassium channels, which regulate in part intracellular calcium levels, was measured by the binding of [3H]glyburide. Scatchard analyses generated a KD for whole brain of vehicle-pretreated mice of 288 pM with a Bmax of 694 fmol/mg protein. In the spinal cord the KD was 0.94 nM and the Bmax was 184 fmol/mg protein. Acute morphine decreased the KD in brain and spinal cord with no change in Bmax. Morphine tolerance increased the KD in brain and spinal cord 2.6- and 2.9-fold, respectively, concurrent with 1.6- and 3.4-fold increases in Bmax. Modulation by morphine of glyburide-sensitive binding sites may contribute at least in part to tolerance to morphine via alterations in intracellular calcium levels in neurons.