title: Chronic morphine treatment increases the number, but decreases the affinity of [3H]-U69,593 binding sites in the rat heart.
abstract: In the present study, the effects of chronic morphine treatment on the binding properties of tritiated U69,593, a specific kappa-ligand, in the rat heart were determined. Adult rats were given morphine through osmotic pumps at a rate of 80 micrograms/hour supplemented by daily injection of morphine at increasing doses for 9 days. The increase in colonic temperature to morphine, used as an indicator of development of tolerance in the rat, was measured daily. It was shown that, on day 7 following morphine treatment, the rats developed tolerance to morphine as indicated by an attenuated hyperthermic response to morphine. The [3H]-U69,593 specific binding properties were determined by direct receptor binding assay. The binding sites increased gradually and reached a significantly higher level at day 10. Scatchard analysis showed that both Bmax and Kd increased at day 10 following morphine treatment, indicating an increase in number of sites and a reduction in affinity to the kappa-ligand. Acute morphine injection at a dose of 10 mg/kg did not cause any significant alteration of [3H]-U69,593 binding sites. Two days after withdrawal of morphine, the [3H]-U69,593 binding sites returned to the original level. The finding of the present study indicates that there is an up-regulation of number, but a reduction in affinity of kappa-binding sites following chronic morphine treatment.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Hong Kong.
authors.forename: Q
authors.initials: Q
authors.lastname: Xia
authors.forename: K K
authors.initials: KK
authors.lastname: Tai
authors.forename: T M
authors.initials: TM
authors.lastname: Wong
mesh_terms: D000818:Animals; D044482:Benzeneacetamides; D001665:Binding Sites; D001831:Body Temperature / Q000187:drug effects; D007700:Kinetics; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D011759:Pyrrolidines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D017473:Receptors, Opioid, kappa; D013997:Time Factors
chemical_list: D044482:Benzeneacetamides; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D009020:Morphine; C045444:U 69593