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 Ki's for mu 2/mu 1 were shown by hemorphin, Tyr-W-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 mu 1 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.
Zadina
J E
JE
VA Medical Center, New Orleans, LA 70146, USA.
Paul
D
D
Gergen
K A
KA
Ge
L J
LJ
Hackler
L
L
Kastin
A J
AJ
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D013788:Thalamus / Q000187:drug effects*
D009292:Narcotic Antagonists; D010455:Peptides; D017450:Receptors, Opioid, mu; C077532:tyrosyl-prolyl-tryptophyl-glycinamide; D009075:MSH Release-Inhibiting Hormone