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

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• 作者：Andrá ; s Z. Ró ; nai ; Mahmoud Al-Khrasani ; Sá ; ndor Benyhe ; Imre Lengyel ; Lá ; szló ; Kocsis ; Gyö ; rgy Orosz ; Gé ; za Tó ; th ; Erzsé ; bet Kató ; and Lá ; szló ; Tó ; t
• 关键词：Endomorphin derivatives ; Partial agonism ; Residual receptor fraction ; β ; -Funaltrexamine ; Mouse vas deferens ; Null and operational model
• 刊名：Peptides
• 出版年：2006
• 出版时间：June 2006
• 年：2006
• 卷：27
• 期：6
• 页码：1507-1513
• 全文大小：189 K

文摘

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.