Opioid peptides: Simultaneous δ agonism and μ antagonism in somatostatin analogues

G. Gregg Bonner; Peg Davis; Dagmar Stropova; Ron Ferguson; Henry I. Yamamura; Frank Porreca; Victor J. Hruby

doi:10.1016/S0196-9781(96)00242-2

Opioid peptides: Simultaneous δ agonism and μ antagonism in somatostatin analogues

G. Gregg Bonner, Peg Davis, Dagmar Stropova, Ron Ferguson, Henry I. Yamamura, Frank Porreca, Victor J. Hruby

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Four isomers of the Somatostatin analogue H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH₂ (CTAP) were made with β-MePhe in position 1 and assayed for opioid binding in rat brain, biological activity in MVD and GPI bioassays, and antinociception in mouse warm-water tail flick assays. These analogues displayed varying potencies and biological activities including: simultaneous δ receptor agonism/μ receptor antagonism, μ receptor antagonism, and δ receptor agonism. These analogues demonstrated that the N-terminal residue is important for receptor potency/selectivity and signal transduction. These analogues may represent leads to therapeutic agents that yield analgesia via δ agonist effects, yet lack side effects associated with μ activity.

Original language	English (US)
Pages (from-to)	93-100
Number of pages	8
Journal	Peptides
Volume	18
Issue number	1
DOIs	https://doi.org/10.1016/S0196-9781(96)00242-2
State	Published - 1997

Keywords

CTAP
GPI
MVD
agonist
analgesia
antagonist
antinocic eption
convulsions
opioid
somatostatin
β-MePhe

ASJC Scopus subject areas

Biochemistry
Physiology
Endocrinology
Cellular and Molecular Neuroscience

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10.1016/S0196-9781(96)00242-2

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title = "Opioid peptides: Simultaneous δ agonism and μ antagonism in somatostatin analogues",

abstract = "Four isomers of the Somatostatin analogue H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) were made with β-MePhe in position 1 and assayed for opioid binding in rat brain, biological activity in MVD and GPI bioassays, and antinociception in mouse warm-water tail flick assays. These analogues displayed varying potencies and biological activities including: simultaneous δ receptor agonism/μ receptor antagonism, μ receptor antagonism, and δ receptor agonism. These analogues demonstrated that the N-terminal residue is important for receptor potency/selectivity and signal transduction. These analogues may represent leads to therapeutic agents that yield analgesia via δ agonist effects, yet lack side effects associated with μ activity.",

keywords = "CTAP, GPI, MVD, agonist, analgesia, antagonist, antinocic eption, convulsions, opioid, somatostatin, β-MePhe",

author = "Bonner, {G. Gregg} and Peg Davis and Dagmar Stropova and Ron Ferguson and Yamamura, {Henry I.} and Frank Porreca and Hruby, {Victor J.}",

note = "Funding Information: This work was supported by grants from NIDA Grant 06284, and U.S. Public Health Service Grant, NS 19972. We thank Dr. Dinesh Patel and Dr. Guigen Li for the synthesis of β-methylphenylalanine.",

year = "1997",

doi = "10.1016/S0196-9781(96)00242-2",

language = "English (US)",

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pages = "93--100",

journal = "Peptides",

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T2 - Simultaneous δ agonism and μ antagonism in somatostatin analogues

AU - Bonner, G. Gregg

AU - Davis, Peg

AU - Stropova, Dagmar

AU - Ferguson, Ron

AU - Yamamura, Henry I.

AU - Porreca, Frank

AU - Hruby, Victor J.

N1 - Funding Information: This work was supported by grants from NIDA Grant 06284, and U.S. Public Health Service Grant, NS 19972. We thank Dr. Dinesh Patel and Dr. Guigen Li for the synthesis of β-methylphenylalanine.

PY - 1997

Y1 - 1997

N2 - Four isomers of the Somatostatin analogue H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) were made with β-MePhe in position 1 and assayed for opioid binding in rat brain, biological activity in MVD and GPI bioassays, and antinociception in mouse warm-water tail flick assays. These analogues displayed varying potencies and biological activities including: simultaneous δ receptor agonism/μ receptor antagonism, μ receptor antagonism, and δ receptor agonism. These analogues demonstrated that the N-terminal residue is important for receptor potency/selectivity and signal transduction. These analogues may represent leads to therapeutic agents that yield analgesia via δ agonist effects, yet lack side effects associated with μ activity.

AB - Four isomers of the Somatostatin analogue H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) were made with β-MePhe in position 1 and assayed for opioid binding in rat brain, biological activity in MVD and GPI bioassays, and antinociception in mouse warm-water tail flick assays. These analogues displayed varying potencies and biological activities including: simultaneous δ receptor agonism/μ receptor antagonism, μ receptor antagonism, and δ receptor agonism. These analogues demonstrated that the N-terminal residue is important for receptor potency/selectivity and signal transduction. These analogues may represent leads to therapeutic agents that yield analgesia via δ agonist effects, yet lack side effects associated with μ activity.

KW - CTAP

KW - GPI

KW - MVD

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KW - analgesia

KW - antagonist

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KW - somatostatin

KW - β-MePhe

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Opioid peptides: Simultaneous δ agonism and μ antagonism in somatostatin analogues

Abstract

Keywords

ASJC Scopus subject areas

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