Chronic morphine upregulates a mu-opiate binding site labeled by [3H]cycloFOXY: a novel opiate antagonist suitable for positron emission tomography.
CycloFOXY (17-cyclopropylmethyl-3,14-dihydroxy-4,5-alpha-epoxy-6-beta- fluoromorphinan) is a novel opiate antagonist synthesized as a ligand suitable for in vivo visualization of opiate receptors using positron emission transaxial tomography. In this paper we report that [3H]cycloFOXY labels two distinct opiate binding sites in rat brain membranes, tentatively identified as mu and kappa. Furthermore, chronic administration of morphine results in a selective up-regulation of the mu binding site. The implications of this finding for models of the opioid receptors and the mechanism of the sodium effect are discussed.
Rothman
R B
RB
Laboratory of Preclinical Pharmacology, St. Elizabeths Hospital, NIMH, Washington, DC 20032.
McLean
S
S
Bykov
V
V
Lessor
R A
RA
Jacobson
A E
AE
Rice
K C
KC
Holaday
J W
JW
D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004361:Drug Tolerance; D004743:Enkephalin, Leucine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu; D014055:Tomography, Emission-Computed
D000477:Alkylating Agents; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009270:Naloxone; D004743:Enkephalin, Leucine; D009271:Naltrexone; D009020:Morphine; C043394:3-acetyl-6-deoxy-6-fluoronaltrexone