alpha N-acetyl derivatives of beta-endorphin-(1-31) and -(1-27) regulate the supraspinal antinociceptive activity of different opioids in mice.

alpha N-acetyl human beta-endorphin-(1-31) injected icv to mice antagonized the analgesic activity of beta-endorphin-(1-31) and morphine whereas the analgesia evoked by DADLE and DAGO was enhanced by this treatment. The modulatory activity of alpha N-acetyl beta-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 alpha N-acetyl human beta-endorphin-(1-31) was partially retained by the shorter peptide alpha N-acetyl human beta-endorphin-(1-27) and to a lesser extent by beta-endorphin-(1-27), beta-endorphin-(1-31) lacked this regulatory activity on opioid analgesia. Acetylated beta-endorphin-(1-31) displayed a biphasic curve when competing with 5 pM [125I]-Tyr27 human beta-endorphin-(1-31) specific binding, the first step (20 to 30% of the binding) was abolished with an apparent IC50 of 0.35 nM, and the rest with an IC50 of 200 nM. It is suggested that alpha N-acetyl beta-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/Go.