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KMID : 0376419960200020133
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Chonbuk University Medical Journal
1996 Volume.20 No. 2 p.133 ~ p.144
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Characterization of Opioid Receptor Binding and Function of a Novel Opioid Ligand, HN-6305
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Abstract
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In an series of effort to develop newer opioidm we compared HN-6305, a Diels-Alder adduct of C19-benzyl thebaine, with Tyr-D-Ala-Gly-(Me) Phe-Gly-ol (DAMGO), a selective agonist for opioid μ receptors, in their receptor binding and effects on
the
high
potassium (20mM)-evoked release of [³H]DAMGO binding sites. HN-6305 inhibited [³H]DAMGO binding dose-dependently. Bmaxs for DAMGO and HN-6305 were almost identical, indicating HN-6305 is a ligand for μopioid receptors with moderate affinity.
DAMGO
and HN-6305 inhibited high potassium-evoked release of [³H]NE form rat cortex slices with different IC50 values. This discrepancy in their ability to inhibit [³H]DAMGO binding and to inhibit [³H]NE release suggests that there may be the other
receptor(s) which mediate(s) inibitory action in [³H]NE release. We, therefore, evaluated the influences of type-selective pioid antagonists for μ, δ, k receptors. DAMGO and NH-6305 showed similar sensitivity to naloxone, a non-selective
opioid
antagonist, and bremazocine, a μ-and K2 opioid antagonist. DAMGO showed greater sensitivity to naloxone, a μ-preferential opioid antagonist, and D-Trp-Orn-Thr-Pen-Thr-NH2(CTOP) , a selective antagonist for μreceptor, than HN-6305. On the other
hand,
DAMGO and HN-6305 showed similar sensitivity to nor-binaltophimine, a K-antagonist, and bremazocine.
Theses results suggest that HN-6305 is an agonist for opiod μreceptor. It, also, can regulate NE release via activation of opioid receptors.
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KEYWORD
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