Binding of Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2) and related peptides to mu(1) and mu(2) opiate receptors

Two endogenous brain peptides (Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2) and Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2)), a cyclized analog and two fragments of Tyr-W-MIF-1, and hemorphin (Tyr-Pro-Trp-Thr) were tested for binding to mu(1) and mu(2) opiate receptor. All these peptides bound to both mu(1) and mu(2) sites in assays optimized to discriminate these subtypes of the mu opiate receptor in membranes from bovine thalamus. The cyclized analog of Tyr-W-MIF-1, previously shown to have potency near that of Tyr-D-Ala-Gly-N-MePhe-Gly-ol (DAMGO) and morphine in producing analgesia after intracerebroventricular (i.c.v.) injection, bound to mu(1) and mu(2) sites with affinities similar to those of DAMGO. Tyr-W-MIF-1, previously shown to induce analgesia after i.c.v. injection but with much higher potency after intrathecal (i.t.) injection, also bound to both mu(1) and mu(2) sites with an affinity between that of morphiceptin and hemorphin. Although the highest ratios of K-i's for mu(2)/mu(1) were shown by hemorphin, Tyr-MIF-1, and Tyr-W-MIF-1, none of the compounds were significantly different in selectivity. The results indicate that the relatively lower potency of Tyr-W-MIF-1 after i.c.v., compared with i.t. injection, is not due to a lack of binding to pi sites. They suggest that it has relatively high efficacy at mu(2), but low efficacy at mu(1) sites, a possibility that might explain some of the novel properties of these peptides.