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A highly selective ligand for brain δ opiate receptors, a ▿ E Phe 4 ‐enkephalin analog, suppresses μ receptor‐mediated thermal analgesia by morphine
Author(s) -
Shimohigashi Yasuyuki,
Takano Yukio,
Kamiya Hiro-o,
Costa Tommaso,
Herz Albert,
Stammer Charles H.
Publication year - 1988
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(88)80444-7
Subject(s) - dynorphin , receptor , morphine , enkephalin , chemistry , opioid , pharmacology , μ opioid receptor , analgesic , vas deferens , endocrinology , ligand (biochemistry) , opioid receptor , medicine , opioid peptide , biochemistry
[D‐Ala 2 ,(2 R ,3 S )‐▿ E Phe 4 ,Leu 5 ]enkephalin (CP‐OH)[ ▿denoting cyclopropyl; superscript E indicating the E ‐configuration about the cyclopropane ring], a highly selective opioid ligand for δ receptors in rat brain, but not for those in the mouse vas deferens, was examined for in vivo biological activities by intracerebroventricular administration. CP‐OH (5–20 μg) showed no analgesic activity in the hot plate (51°C) test using rats. However, it suppressed completely the analgesic effects of intraperitoneally administered morphine (3 mg/kg rat) in a dose‐dependent manner. CP‐OH showed no binding affinity for brain κ receptors to which dynorphin, an opioid peptide that inhibits morphine analgesia, binds predominantly. These results suggest that, besides the conventional δ receptors which mediate analgesia, the rat brain contains another δ‐like receptor which has a modulatory role to attenuate morphine‐induced analgesia mediated through the μ receptors, and that this modulatory receptor does not exist in the mouse vas deferens.