A highly selective ligand for brain δ opiate receptors, a ▿E Phe4‐enkephalin analog, suppresses μ receptor‐mediated thermal analgesia by morphine

FEBS Letters

Herz, Albert⁴  Stammer, Charles H.²  Takano, Yukio³  Costa, Tommaso⁴  Kamiya, Hiro-o³  Shimohigashi, Yasuyuki¹ 

[1] Laboratory of Biochemistry, Faculty of Science, Kyushu University 33, Fukuoka 812, Japan;Department of Chemistry, School of Chemical Sciences, University of Georgia, Athens, GA 30602, USA;Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-01, Japan;Laboratory of Neuropharmacology, Max-Planck-Institute for Psychiatry, D-8033 Martinsried, FRG

关键词: Opiate receptor;    Analgesia;    Antagonism;    Enkephalin analog;    Receptor heterogeneity;   

DOI  :  10.1016/0014-5793(88)80444-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

[D-Ala²,(2R,3S)-▿ ^E Phe⁴,Leu⁵]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.

【 授权许可】

Unknown