Irreversible binding of cis-(+)-3-methylfentanyl isothiocyanate to the delta opioid receptor and determination of its binding domain.

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Zhu J, Yin J, Law PY, Claude PA, Rice KC, Evans CJ, Chen C, Yu L, Liu-Chen LY

Irreversible binding of cis-(+)-3-methylfentanyl isothiocyanate to the delta opioid receptor and determination of its binding domain.

J Biol Chem. 1996 Jan 19;271(3):1430-4.

PubMed ID

8576134 [ View in PubMed

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Abstract

Binding of cis-(+)-3-methylfentanyl isothiocyanate (SUPERFIT) to cloned opioid receptors stably expressed in Chinese hamster ovary cells was characterized. SUPERFIT inhibited [3H]diprenorphine binding with much higher affinity for the delta than the mu or kappa receptor. Pretreatment with SUPERFIT followed by extensive washing reduced delta binding with an IC50 value of 7.1 nM, yet it did not affect mu and kappa binding up to 0.1 microns. The reduction in delta binding by SUPERFIT pretreatment was due to a decrease in Bmax with no change in Kd. These results indicate that SUPERFIT is a highly selective delta irreversible ligand. We then determined the region in the delta receptor that confered binding selectivity for SUPERFIT by examining its binding to six mu/delta chimeric receptors. SUPERFIT bound to delta, mu/delta 1 (amino acids mu 1-94/delta 76-372), delta/mu 3 (delta 1-134/mu 154-398), and delta/mu 4 (delta 1-187/mu 207-398) receptors with high affinity but to mu, delta/mu 1 (delta 1-75/mu 95-398), mu/delta 3 (mu 1-153/delta 135-372), and mu/delta 4 (mu 1-206/delta 188-372) receptors with low affinity. Pretreatment with SUPERFIT potently inhibited [3H]diprenorphine binding to delta, mu/delta 1, delta/mu 3, and delta/mu 4 but affected binding to mu, delta/mu 1, mu/delta 3, and mu/delta 4 only at much higher concentrations. Thus, the segment from the beginning of the first intracellular loop to the middle of the third transmembrane helix of the delta receptor is important for selective binding of SUPERFIT.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
3-Methylfentanyl	Delta-type opioid receptor	Protein	Humans	Yes	Agonist	Details
3-Methylfentanyl	Kappa-type opioid receptor	Protein	Humans	Yes	Agonist	Details
3-Methylfentanyl	Mu-type opioid receptor	Protein	Humans	Yes	Agonist	Details