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 membranes from normal ICR mice, glucose (100-400 mg/dl) caused small but significant concentration-dependent decreases in receptor affinities for [3H]naloxone and [3H]dihydromorphine, both in the absence and presence of 20 mM NaCl, without changing the maximum number of binding sites. Fructose and the nonmetabolizable sugar 3-O-methylglucose had intermediate effects on naloxone affinity in the presence of NaCl 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 NaCl 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+) littermates. 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.
Brase
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DA
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Han
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YH
Dewey
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WL
D019325:3-O-Methylglucose; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004090:Dihydromorphine / Q000378:metabolism*; D005632:Fructose / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D008297:Male; D008757:Methylglucosides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009022:Morphine Derivatives / Q000378:metabolism*; D009270:Naloxone / Q000378:metabolism*; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology
D008757:Methylglucosides; D009022:Morphine Derivatives; D011957:Receptors, Opioid; D019325:3-O-Methylglucose; D005632:Fructose; D009270:Naloxone; D012965:Sodium Chloride; D004090:Dihydromorphine; D005947:Glucose