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 Citations (Scopus)

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
Externally publishedYes

Fingerprint

D-Penicillamine (2,5)-Enkephalin
delta Opioid Receptor
Vas Deferens
Cyclic Peptides
Peptides
Opioid Peptides
Narcotic Antagonists
Bioassay
Enkephalins
Opioid Receptors
Biological Assay

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Extraordinary potency of a novel delta opioid receptor agonist is due in part to increased efficacy. / Kramer, Thomas H.; Bartosz-Bechowski, Hubert; Davis, Peg; Hruby, Victor J; Porreca, Frank.

In: Life Sciences, Vol. 61, No. 2, 06.06.1997, p. 129-135.

Research output: Contribution to journalArticle

Kramer, Thomas H. ; Bartosz-Bechowski, Hubert ; Davis, Peg ; Hruby, Victor J ; Porreca, Frank. / Extraordinary potency of a novel delta opioid receptor agonist is due in part to increased efficacy. In: Life Sciences. 1997 ; Vol. 61, No. 2. pp. 129-135.
@article{0708685f305b48958d5566260a451645,
title = "Extraordinary potency of a novel delta opioid receptor agonist is due in part to increased efficacy",
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.",
keywords = "Agonist efficacy, Bioassay, Delta opioid receptors, Vas deferens",
author = "Kramer, {Thomas H.} and Hubert Bartosz-Bechowski and Peg Davis and Hruby, {Victor J} and Frank Porreca",
year = "1997",
month = "6",
day = "6",
doi = "10.1016/S0024-3205(97)00367-6",
language = "English (US)",
volume = "61",
pages = "129--135",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Extraordinary potency of a novel delta opioid receptor agonist is due in part to increased efficacy

AU - Kramer, Thomas H.

AU - Bartosz-Bechowski, Hubert

AU - Davis, Peg

AU - Hruby, Victor J

AU - Porreca, Frank

PY - 1997/6/6

Y1 - 1997/6/6

N2 - 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.

AB - 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.

KW - Agonist efficacy

KW - Bioassay

KW - Delta opioid receptors

KW - Vas deferens

UR - http://www.scopus.com/inward/record.url?scp=0030969093&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030969093&partnerID=8YFLogxK

U2 - 10.1016/S0024-3205(97)00367-6

DO - 10.1016/S0024-3205(97)00367-6

M3 - Article

C2 - 9217271

AN - SCOPUS:0030969093

VL - 61

SP - 129

EP - 135

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 2

ER -