αN-acetyl derivatives of β-endorphin-(1-31) and -(1-27) regulate the supraspinal antinociceptive activity of different opioids in mice

αN-acetyl human β-endorphin(1-31) injected icv to mice antagonized the analgesic activity of β-endorphin-(1-31) and morphine whereas the analgesia evoked by DADLE and DAGO was enhanced by this treatment. The modulatory activity of αN-acetyl β-endorphin-(1-31) was exhibited at remarkable low doses (fmols) reaching a maximum that persisted even though the dose was increased 100,000 times. The regulatory effect of a single dose of the acetylated neuropeptide lasted for 24h. The activity of αN-acetyl human β-endorphin(1-31) was partially retained by the shorter peptide αN-acetyl human β-endorphin-(1-27) and to a lesser extent by β-endorphin-(1-27), β-endorphin-(1-31) lacked this regulatory activity on opioid analgesia. Acetylated β-endorphin-(1-31) displayed a biphasic curve when competing with 5 pM [125I]-Tyr27 human β-endorphin-(1-31) specific binding, the first step was abolished with an apparent IC50 of 0.35 nM, and the rest with an IC50 of 200 nM. It is suggested that αN-acetyl β-endorphin-(1-31) changed the efficiency of the opioid analgesics by acting upon a specific substrate that is functionally coupled to the opioid receptor, presumably the guanine nucleotide binding regulatory proteins Gi/G0