Structure-activity relationships of analogs of the endogenous brain peptides Tyr-MIF-1 and Tyr-W-MIF-1.
Analogs of the naturally occurring peptides Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) and Tyr-W-MIF-1 (Tyr-Pro-Trp-GLy-NH2) were synthesized and investigated for their opiate agonist as well as antagonist activity in the guinea pig ileum assay. [Tyr5]-Tyr-MIF-1 and the endogenous Tyr-W-MIF-1 were the most potent opiate agonists among the 20 compounds tested. Several analogs showed antiopiate activity in the ileum from morphine-tolerant animals as measured by attenuation of the agonistic effect of DAMGO, which inhibits electrically stimulated contractions of the ileum. The binding activity of the analogs at mu opiate receptors was determined by displacement of [3H]-DAMGO in rat brain. Tyr-W-MIF-1 and its analogs were more potent than Tyr-MIF-1 and its analogs in this binding assay. Thus, Tyr-MIF-1, Tyr-W-MIF-1 and several of their analogs could act as opiate agonists as well as antagonists.
Erchegyi
J
J
VA Medical Center, New Orleans, LA 70146.
Zadina
J E
JE
Qiu
X D
XD
Kersh
D C
DC
Ge
L J
LJ
Brown
M M
MM
Kastin
A J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009292:Narcotic Antagonists / Q000737:chemistry / Q000494:pharmacology; D011863:Radioimmunoassay; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013329:Structure-Activity Relationship
D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; C077532:tyrosyl-prolyl-tryptophyl-glycinamide; C036930:tyrosyl-prolyl-leucyl-glycinamide; D009075:MSH Release-Inhibiting Hormone