Modification of opioid receptors and uncoupling of receptors from G proteins as possible mechanisms underlying suppression of opioid binding by cholecystokinin octapeptide.
Previous studies have shown that central cholecystokinin (CCK) octapeptide (CCK-8) suppresses the binding of opioid receptors to the opioid agonists. In the present study, tritium-labelled etorphine (opioid agonist) and naloxone (opioid antagonist) as well as guanosine-5'-0-(3-thiotriphosphate) (GTPrS) were used to investigate the possible mechanisms underlying the suppression of opioid binding by CCK-8 in rat brain membranes. CCK-8 at a concentration range of 10 nmol/L to 1 mumol/L dose-dependently suppressed the binding of [3H]-naloxone to opioid receptors, with a decrease in Bmax and an increase in Kd. GTPrs was found to reduce the affinity of [3H]-etorphine binding in a dose-dependent manner. This effect was markedly diminished in the presence of 10 nmol/L of CCK-8. These results suggest that CCK-8 might suppress opioid binding at both the receptor and post-receptor levels; that is, 1) by reducing the number and affinity of opioid receptors, and 2) by uncoupling opioid receptors from their G proteins.
Zhang
L
L
Neuroscience Research Center, Beijing Medical University.
Wang
X
X
Han
J
J
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005048:Etorphine / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology*
D011957:Receptors, Opioid; D009270:Naloxone; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D005048:Etorphine; D019204:GTP-Binding Proteins; D012844:Sincalide