Morphine tolerance-induced modulation of [H-3]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 [H-3]glyburide. Scatchard analyses generated a K-D for whole brain of vehicle-pretreated mice of 288 pM with a B-max of 694 fmol/mg protein. In the spinal cord the K-D was 0.94 nM and the B-max was 184 fmol/mg protein. Acute morphine decreased the K-D in brain and spinal cord with no change in B-max. Morphine tolerance increased the K-D in brain and spinal cord 2.6- and 2.9-fold, respectively, concurrent with 1.6- and 3.4-fold increases in B-max. 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. (C) 1997 Elsevier Science Ireland Ltd.