A novel non-Opioid binding site for endomorphin-1

摘要: Endomorphins are natural amidated opioid tetrapeptides with the following structure: Tyr-Pro-Trp-Phe-NH2 (endomorphin-1), and Tyr-Pro-Phe-Phe-NH2 (endomorphin-2). interact selectively μ-opioid or MOP receptors exhibit nanomolar sub-nanomolar receptor binding affinities, therefore they suggested to be endogenous agonists for receptors. mediate a number of characteristic effects, such as antinociception, however there several physiological functions in which endomorphins appear act fashion that does not involve activation receptor. Our recent data indicate radiolabelled [3H]endomorphin-1 specific radioactivity 2.35 TBq/mmol - prepared by catalytic dehalogenation diiodinated peptide precursor presence tritium gas is able bind second, naloxone insensitive recognition site rat brain membranes. Binding heterogeneity, i.e., higher (Kd = 0.4 nM / Bmax 120 fmol/mg protein) lower 8.2 432 affinity components observed both saturation experiments followed Schatchard analysis, equilibrium competition studies. The signs multiplicity, e.g., curvilinear plots biphasic displacement curves seen only if non-specific measured excess unlabeled endomorphin-1 naloxone. non-opioid recognized heterocyclic alkaloid ligands, neither morphine, nor antagonists On contrary, displaced from its affinity, capacity neuropeptides, including methionine-enkephalin-Arg-Phe, nociceptin-orphanin FQ, angiotensin FMRF-amide. This naloxone-insensitive, consequently seems present nervous tissues carrying low density no receptors, rodent cerebellum, deficient (MOPr-/-) transgenic 'knock-out' (K.O.) mice. newly described component coupled regulatory G-proteins, it affect adenylyl cyclase enzyme activity. Taken together carries and, addition needs taken into account when various effects evaluated pathologic conditions.