H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2: a potent and selective antagonist opioid receptors.

K. Gulya, G. K. Lui, J. T. Pelton, W. Kazmierski, V. J. Hruby, H. I. Yamamura

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Abstract

H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) exhibited high affinity (IC50 = 2.80 nM) in displacing [3H]naloxone binding (nH = 0.89 +/- 0.1) and showed an exceptional selectivity for mu opioid receptors with an IC50(DPDPE)/IC50(naloxone) ratio of 4,840, while it displayed very low affinity for somatostatin receptors (IC50 = 22,700 nM) in rat brain binding assays. [3H]CTOP was recently custom synthesized (spec. act.: 84 Ci/mmol) and evaluated for its in vitro binding properties towards the mu opioid receptors in rat brain membrane preparations. Association and dissociation of [3H]CTOP binding to mu opioid receptors were rapid at 25 degrees C with a kinetic Kd value of 0.67 nM. Saturation experiments gave apparent Kd value of 1.11 nM and Bmax value of 136 +/- 13 fmol/mg prot at 25 degrees C. Specific [3H]CTOP binding was inhibited by a number of different opioid and opiate ligands. Among them, putative mu opioid receptor-specific ligands, such as naloxone, naltrexone and CTOP inhibited the binding with high affinity, while delta opioid receptor-specific compounds or non-opioid drugs inhibited specific [3H]CTOP binding with low affinity or they were ineffective.

Original languageEnglish (US)
Pages (from-to)209-212
Number of pages4
JournalNIDA research monograph
Volume75
StatePublished - 1986

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ASJC Scopus subject areas

  • Medicine (miscellaneous)

Cite this

Gulya, K., Lui, G. K., Pelton, J. T., Kazmierski, W., Hruby, V. J., & Yamamura, H. I. (1986). H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2: a potent and selective antagonist opioid receptors. NIDA research monograph, 75, 209-212.