Extraordinary potency of a novel delta opioid receptor agonist is due in part to increased efficacy

Thomas H. Kramer, Hubert Bartosz-Bechowski, Peg Davis, Victor J. Hruby, Frank Porreca

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

A new cyclic opioid peptide of sequence Tyr-D-Pen-Gly-Phe-Cys-Phe (HBP2) was examined in the mouse isolated vas deferens (MVD) bioassay. Studies with receptor-selective opioid antagonists showed the peptide to be highly selective for σ opioid receptors. HBP2 and the standard σ agonist DPDPE were simultaneously compared using the technique of partial irreversible receptor blockade; data were analyzed using the operational model of pharmacologic agonism. HBP2 was approximately 160 times as potent as DPDPE; estimation of the affinity and efficacy of the two peptides revealed that the potency increase was due to a 5.3-fold increase in efficacy, as well as a 37-fold increase affinity. This contrasts with our previous findings with other cyclic enkephalin analogs, in which increased affinity was achieved without a change in apparent efficacy. Analysis of concentration-response curve shape suggested in addition the possibility of heterogeneity in transduction mechanism for MVD σ receptors.

Original languageEnglish (US)
Pages (from-to)129-135
Number of pages7
JournalLife Sciences
Volume61
Issue number2
DOIs
StatePublished - Jun 6 1997

Keywords

  • Agonist efficacy
  • Bioassay
  • Delta opioid receptors
  • Vas deferens

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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