Discrimination of a novel type of rat brain delta opioid receptors by enkephalin analog containing structurally constrained cyclopropylphenylalanine (inverted delta Phe).
Four different stereoisomers of cyclopropylphenylalanine (inverted delta Phe) were incorporated into [D-Ala2,Leu5]enkephalin at the position 4. These conformationally restricted enkephalin analogs were evaluated for their binding characteristics to mu and delta opioid receptors in rat brain. A striking finding is that the E-(2R,3S)-isomer binds to a novel class of delta receptors and discriminates this receptor from the ordinary delta receptor. This new type of delta receptor suspected to be a receptor which suppresses the thermal analgesia mediated through mu receptor. The Z-(2R,3R)-isomer was very potent with several times more enhanced affinity to delta receptors than to mu receptors, but could not differentiate the delta receptors. The Z-(2S,3S)-isomer was weak, and E-(2S,3R)-isomer was almost inactive.
Chuman
Y
Y
Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka, Japan.
Yasunaga
T
T
Costa
T
T
Shimohigashi
Y
Y
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003521:Cyclopropanes / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007536:Isomerism; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D003521:Cyclopropanes; D004745:Enkephalins; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C051120:cyclopropylphenylalanine; D010649:Phenylalanine