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.
Welch
S P
SP
Department of Pharmacology and Toxicology, Medical College of Virginia, Richmond 23298-0613, USA.
Smith
F L
FL
Dewey
W L
WL
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004343:Drug Implants; D004361:Drug Tolerance; D005905:Glyburide / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000378:metabolism*; D007279:Injections, Subcutaneous; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D004343:Drug Implants; D007004:Hypoglycemic Agents; D009294:Narcotics; D015221:Potassium Channels; D009020:Morphine; D000255:Adenosine Triphosphate; D005905:Glyburide; D002118:Calcium