(35)S]GTPgammaS binding stimulated by endomorphin-2 and morphiceptin analogs |
| |
Authors: | Fichna Jakub do-Rego Jean-Claude Kosson Piotr Schiller Peter W Costentin Jean Janecka Anna |
| |
Institution: | Laboratory of Biomolecular Chemistry, Institute of Biomedicinal Chemistry, Medical University, Lodz, Poland. |
| |
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. |
| |
Keywords: | μ-Opioid receptor ligand Agonist Antagonist Rat thalamus G protein-coupled receptor Functional assay |
本文献已被 ScienceDirect PubMed 等数据库收录! |