Effects of Glucose and Diabetes on Binding of Naloxone and Dihydromorphine to Opiate Receptors in Mouse Brain

The effects of glucose and diabetes on the high-affinity lofentanil-displaceable opiate-receptor binding in mouse brain membranes were studied to determine if the attenuation of opiate actions by hyperglycemia previously observed in our laboratory was due to a modification of receptor affinity or number. With embranes from normal ICR mice, glucose (100–400 mg/dl) caused small but significant concentrationdependent decreases in receptor affinities for [³H]naloxone and [³H]dihydromorphine, both in the absence and presence of 20 mM NaCI, without changing the maximum number of binding sites. Fructose and the nonmetabolizable sugar 3-O-methylglucose had intermedi ate effects on naloxone affinity in the presence of NaCI that were not significantly different from control or from the effect of glucose. Similar results were obtained with brain membranes from streptozocin-induced diabetic mice. The binding affinity for [³H]naloxone in the presence of NaCI was not affected by the induction of diabetes in ICR mice via streptozocin or in spontaneously diabetic (db/db) C57BL/KsJ mice compared with their nondiabetic (m⁺/m⁺) litter mates. These results indicate that the previously observed attenuation of opiate effects by glucose may be partly due to a glucose-induced decrease in opiate-receptor affinity. However, the much greater attenuation of morphine by fructose in vivo cannot be explained by this mechanism.