Teruo Yasunaga

Discrimination of a novel type of rat brain δ opioid receptors by enkephalin analog containing structurally constrained cyclopropylphenylalanine (∇Phe)

Four different stereoisomers of cyclopropylphenylalanine (∇Phe) were incorporated into [D‐Ala2,Leu5]enkephalin at the position 4. These conformationally restricted enkephalin analogs were evaluated for their binding characteristics to μ and δ opioid receptors in rat brain. A striking finding is that the E‐(2R,3S)‐isomer binds to a novel class of δ receptors and discriminates this receptor from the ordinary δ receptor. This new type of δ receptor suspected to be a receptor which suppresses the thermal analgesia mediated through μ receptor. The Z‐(2R,3R)‐isomer was very potent with several times more enhanced affinity to δ receptors than to μ receptors, but could not differentiate the δ receptors. The Z‐(2S,3S)‐isomer was weak, and E‐(2S,3R)‐isomer was almost inactive.