Journal
PEPTIDES
Volume 26, Issue 7, Pages 1159-1166Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2005.01.018
Keywords
nociceptin; NOP receptor; radiopharmaceutical; DTPA chelate; radioligand binding; GTP gamma S assay; mouse vas deferens bioassay
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Nociceptin is an endogenous anti-opiate heptadecapeptide primarily interacting with the nociceptin (NOP) receptor. This neuropeptide-receptor system is involved in pain regulation, tolerance to and dependence on opiates as well as many other physiological and pathophysiological events. The role and mechanisms of nociceptin in pathological conditions is not clearly known yet. In an attempt to have a radiopharmaceutical labeled either with Tc-99m or In-111, we incorporated diethylenetriaminepentaacetic acid (DTPA) as chelator into the structure of [Arg(14), Lys(15)]nociceptin(1- 17)-NH2 at the e-amino group of Lys(15). Such a radiopeptide may be useful in imaging for diagnostical purposes. Preparation of the peptide ligands was carried out by solid phase synthesis. Two peptides containing DTPA were obtained and purified. The products were [Arg(14), Lys(DTPA)(15)]nociceptin(1-17)-NH2 and its cross-linked dimer on the basis of mass spectrometric analysis. In In-115(3+) binding experiments the conjugates exhibited preserved indium ion chelating properties, indicating the potential use of radiolabeled DTPA-nociceptin derivatives as radiopharmaceutical. Biological properties of these compounds were studied in rat brain membrane preparations by radioligand binding, functional biochemical [S-35]GTP gamma S binding assays and mouse vas deferens (MVD) bioassay. Besides the similar in vitro binding characteristics to nociceptin receptor, both of the DTPA-chelated compounds were more potent and efficient than nociceptin in functional biochemical and mouse vas deferens bioassays. Our further aim is to radiolabel these compounds in order to get a radiopharmaceutical which can be used diagnostically. (c) 2005 Elsevier Inc. All rights reserved.
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