Receptor selectivity of Met-enkephalin-Arg6-Phe7, an endogenous opioid peptide, in cerebral cortex of human and rat☆

Abstract This study was undertaken to examine the receptor selectivity of Met-enkephalin-Arg 6 -Phe 7 (MERF) employing radioreceptor binding assays in human cerebral cortex membranes, and to elucidate the responsible receptors that mediate the regulatory action of MERF on high (20 mM) K + -stimulated release of [ 3 H]norepinephrine ([ 3 H]-NE) in rat cortex slices. Specific binding of [ 3 H]MERF was inhibited by DAMGO, Tyr-D-Arg-Phe-Sar(TAPS), bremazocine and ethylketocyclazocine (EKC), but not by U69,593 (U69) and DPDPE. MERF showed high affinity for specific binding sites of [ 3 H]DAMGO. However, MERF had little influence on the specific binding of [ 3 H]DPDPE, [ 3 H]U69 and [ 3 H]diprenorphine ([ 3 H]DIP) in the presence of 1 μM each of DAMGO, DPDPE and U69. In [ 3 H]NE release experiments using rat cortex slices, DAMGO, MERF and EKC, in order of their potency, inhibited K + -stimulated release of [ 3 H]NE. The inhibitory effects of MERF and DAMGO were more sensitive than that of EKC to antagonism by CTAP, nor-binaltorphimine (nor-BNI) and naloxone. These results suggested that MERF possesses high affinity for μ-receptors, but not for δ-, κ 1 -, and very low affinity for κ 2 -receptors in human cerebral cortex membranes. Also, the inhibitory effect of MERF on the K + -stimulated release of [ 3 H]NE appears to be mediated by μ-receptors in rat cerebral cortex slices.