Opioid and antiopioid actions of Tyr-MIF-1, Tyr-W-MIF-1 and hemorphin-4 on rat locus coeruleus neurons: intracellular recording in vitro

Intracellular recording was used to study the effects of naturally occurring opioid tetrapeptides, including Tyr-Pro-Leu-Gly-NH2 (Tyr-MIF-1), Tyr-Pro-Trp-Gly-NH2 (Tyr-W-MIF-1), and Tyr-Pro-brain slice preparation. These tetrapeptides which, like other opioids, caused inhibitory effects on all LC neurons tested. Tyr-MIF-1 (10-100 microM), Tyr-W-MIF-1 (1-10 microM) and hemorphin-4 (1-30 microM) caused dose-related inhibition of the spontaneous firing. The IC50 were 37.5, 3.8 and 6.7 microM for Tyr-MIF-1, Tyr-W-MIF-1 and hemorphin-4, respectively. In addition, these tetrapeptides were tested for their blocking effects on the Tyr-D-Arg-Phe-sarcosine-OH (TAPS)-induced inhibitory actions. The results showed that Tyr-MIF-1, Tyr-W-MIF-1 and hemorphin-4 significantly decreased the actions of lower concentration of TAPS (30 nM), but did not decrease the actions of higher concentration of TAPS (100 nM). It is concluded that the blood-derived peptide hemorphin-4 and the endogenous Peptides Tyr-W-MIF-1 and Tyr-MIF-1 possess opioid and antiopioid actions in the LC neurons.