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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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
Pages (from-to)209-212
Number of pages4
JournalNIDA research monograph
Volume75
Publication statusPublished - 1986

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Narcotic Antagonists
mu Opioid Receptor
Inhibitory Concentration 50
Naloxone
Opiate Alkaloids
D-Penicillamine (2,5)-Enkephalin
Ligands
Somatostatin Receptors
Naltrexone
delta Opioid Receptor
Brain
Opioid Analgesics
phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide
Membranes
Pharmaceutical Preparations

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.

H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 : a potent and selective antagonist opioid receptors. / Gulya, K.; Lui, G. K.; Pelton, J. T.; Kazmierski, W.; Hruby, V. J.; Yamamura, H. I.

In: NIDA research monograph, Vol. 75, 1986, p. 209-212.

Research output: Contribution to journalArticle

Gulya, K, Lui, GK, Pelton, JT, Kazmierski, W, Hruby, VJ & Yamamura, HI 1986, 'H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2: a potent and selective antagonist opioid receptors.', NIDA research monograph, vol. 75, pp. 209-212.
Gulya, K. ; Lui, G. K. ; Pelton, J. T. ; Kazmierski, W. ; Hruby, V. J. ; Yamamura, H. I. / H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 : a potent and selective antagonist opioid receptors. In: NIDA research monograph. 1986 ; Vol. 75. pp. 209-212.
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