Partial and full agonism in endomorphin derivatives: Comparison by null and operational model

András Z. Rónai; Mahmoud Al-Khrasani; Sándor Benyhe; Imre Lengyel; László Kocsis; György Orosz; Géza Tóth; Erzsébet Kató; László Tóthfalusi

doi:10.1016/j.peptides.2005.12.003

Partial and full agonism in endomorphin derivatives: Comparison by null and operational model

András Z. Rónai^*, Mahmoud Al-Khrasani, Sándor Benyhe, Imre Lengyel, László Kocsis, György Orosz, Géza Tóth, Erzsébet Kató, László Tóthfalusi

^*Corresponding author for this work

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

17 Citations (Scopus)

Abstract

The partial μ-opioid receptor pool inactivation strategy in isolated mouse vas deferens was used to determine partial agonism of endomorphins and their analogs (endomorphin-1-ol, 2′,6′-dimethyltyrosine (Dmt)-endomorphin-1, endomorphin-2-ol and (d-Met²)-endomorphin-2) using morphine, normorphine, morphiceptin, (d-Ala²,MePhe⁴,Gly⁵-ol)-enkephalin (DAMGO) and its amide (DAMGA) as reference opioid agonists. Agonist affinities (K_A) and efficacies were assessed both by the "null" and the "operational" method. The K_A values determined by the two methods correlated significantly with each other and also with the displacing potencies against ³H-naloxone in the receptor binding assay in the presence of Na⁺. DAMGO and DAMGA were full agonist prototypes, morphine, endomorphin-1, endomorphin-1-ol, Dmt-endomorphin-1, endomorphin-2-ol and (d-Met²)-endomorphin-2 were found by both methods to be partial agonists whereas the parameters for normorphine, morphiceptin and endomorphin-2 were intermediate.

Original language	English
Pages (from-to)	1507-1513
Number of pages	7
Journal	Peptides
Volume	27
Issue number	6
DOIs	https://doi.org/10.1016/j.peptides.2005.12.003
Publication status	Published - Jun 2006
Externally published	Yes

Keywords

β-Funaltrexamine
Endomorphin derivatives
Mouse vas deferens
Null and operational model
Partial agonism
Residual receptor fraction

ASJC Scopus subject areas

Biochemistry
Physiology
Endocrinology
Cellular and Molecular Neuroscience

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10.1016/j.peptides.2005.12.003

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title = "Partial and full agonism in endomorphin derivatives: Comparison by null and operational model",

abstract = "The partial μ-opioid receptor pool inactivation strategy in isolated mouse vas deferens was used to determine partial agonism of endomorphins and their analogs (endomorphin-1-ol, 2′,6′-dimethyltyrosine (Dmt)-endomorphin-1, endomorphin-2-ol and (d-Met2)-endomorphin-2) using morphine, normorphine, morphiceptin, (d-Ala2,MePhe4,Gly5-ol)-enkephalin (DAMGO) and its amide (DAMGA) as reference opioid agonists. Agonist affinities (KA) and efficacies were assessed both by the {"}null{"} and the {"}operational{"} method. The KA values determined by the two methods correlated significantly with each other and also with the displacing potencies against 3H-naloxone in the receptor binding assay in the presence of Na+. DAMGO and DAMGA were full agonist prototypes, morphine, endomorphin-1, endomorphin-1-ol, Dmt-endomorphin-1, endomorphin-2-ol and (d-Met2)-endomorphin-2 were found by both methods to be partial agonists whereas the parameters for normorphine, morphiceptin and endomorphin-2 were intermediate.",

keywords = "β-Funaltrexamine, Endomorphin derivatives, Mouse vas deferens, Null and operational model, Partial agonism, Residual receptor fraction",

author = "R{\'o}nai, {Andr{\'a}s Z.} and Mahmoud Al-Khrasani and S{\'a}ndor Benyhe and Imre Lengyel and L{\'a}szl{\'o} Kocsis and Gy{\"o}rgy Orosz and G{\'e}za T{\'o}th and Erzs{\'e}bet Kat{\'o} and L{\'a}szl{\'o} T{\'o}thfalusi",

year = "2006",

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doi = "10.1016/j.peptides.2005.12.003",

language = "English",

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T1 - Partial and full agonism in endomorphin derivatives

T2 - Comparison by null and operational model

AU - Rónai, András Z.

AU - Al-Khrasani, Mahmoud

AU - Benyhe, Sándor

AU - Lengyel, Imre

AU - Kocsis, László

AU - Orosz, György

AU - Tóth, Géza

AU - Kató, Erzsébet

AU - Tóthfalusi, László

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AB - The partial μ-opioid receptor pool inactivation strategy in isolated mouse vas deferens was used to determine partial agonism of endomorphins and their analogs (endomorphin-1-ol, 2′,6′-dimethyltyrosine (Dmt)-endomorphin-1, endomorphin-2-ol and (d-Met2)-endomorphin-2) using morphine, normorphine, morphiceptin, (d-Ala2,MePhe4,Gly5-ol)-enkephalin (DAMGO) and its amide (DAMGA) as reference opioid agonists. Agonist affinities (KA) and efficacies were assessed both by the "null" and the "operational" method. The KA values determined by the two methods correlated significantly with each other and also with the displacing potencies against 3H-naloxone in the receptor binding assay in the presence of Na+. DAMGO and DAMGA were full agonist prototypes, morphine, endomorphin-1, endomorphin-1-ol, Dmt-endomorphin-1, endomorphin-2-ol and (d-Met2)-endomorphin-2 were found by both methods to be partial agonists whereas the parameters for normorphine, morphiceptin and endomorphin-2 were intermediate.

KW - β-Funaltrexamine

KW - Endomorphin derivatives

KW - Mouse vas deferens

KW - Null and operational model

KW - Partial agonism

KW - Residual receptor fraction

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EP - 1513

JO - Peptides

JF - Peptides

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ER -

Partial and full agonism in endomorphin derivatives: Comparison by null and operational model

Abstract

Keywords

ASJC Scopus subject areas

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