title: [(35)S]GTPgammaS binding stimulated by endomorphin-2 and morphiceptin analogs.
abstract: The ability of several mu-selective opioid peptides to activate G-proteins was measured in rat thalamus membrane preparations. The mu-selective ligands used in this study were three structurally related peptides, endomorphin-1, endomorphin-2 and morphiceptin, and their analogs modified in position 3 or 4 by introducing 3-(1-naphthyl)-d-alanine (d-1-Nal) or 3-(2-naphthyl)-d-alanine (d-2-Nal). The results obtained for these peptides in [(35)S]GTPgammaS binding assay were compared with those obtained for a standard mu-opioid agonist DAMGO. [d-1-Nal(3)]Morphiceptin was more potent in G-protein activation (EC(50) value of 82.5+/-4.5 nM) than DAMGO (EC(50)=105+/-9 nM). [d-2-Nal(3)]Morphiceptin, as well as endomorphin-2 analogs substituted in position 4 by either d-1-Nal or d-2-Nal failed to stimulate [(35)S]GTPgammaS binding and were shown to be potent antagonists against DAMGO. It seems that the topographical location of the aromatic ring of position 3 and 4 amino acid residues can result in a completely different mode of action, producing either agonists or antagonists.
authors: Laboratory of Biomolecular Chemistry, Institute of Biomedicinal Chemistry, Medical University, Lodz, Poland.
authors: Jakub
authors: J
authors: Fichna
authors: Jean-Claude
authors: JC
authors: do-Rego
authors: Piotr
authors: P
authors: Kosson
authors: Peter W
authors: PW
authors: Schiller
authors: Jean
authors: J
authors: Costentin
authors: Anna
authors: A
authors: Janecka