Abstract：
:The nociceptin receptor (NOP) and its endogenous ligand, nociceptin/orphanin FQ (OFQ), are involved in a wide range of biological functions, such as pain, anxiety, learning, and memory. The zebrafish has been proposed as a candidate to study the in vivo effects of several drugs of abuse and to discover new pharmacological targets. We report the cloning, expression, and pharmacological characterization of a NOP receptor from zebrafish (drNOP). The full-length cDNA codes a protein of 363 residues, which shows high sequence similarity to other NOPs. Phylogenetic analysis indicates that NOPs are broadly conserved during vertebrate evolution, and that they stand for the most divergent clade of the opioid/OFQ receptor family. Expression studies have revealed that drNOP mRNA is highly expressed in the central nervous system, and low expression levels are also found in peripheral tissues such as gills, muscle, and liver. Pharmacological analysis indicates that drNOP displays specific and saturable binding for [Leucyl-3,4,5-(3)H]nociceptin, with a K(d)=0.20 ± 0.02 nM and a B(max)=1703 ± 81 fmol/mg protein. [(3)H]Nociceptin binding is displaced by several opioid ligands such as dynorphin A (DYN A), naloxone, bremazocine, or the κ-selective antagonist nor-binaltorphimine. [(35)S]GTPγS stimulation studies showed that drNOP receptor is functional, as nociceptin is able to fully activate the receptor and DYN A behaves as a partial agonist (50% stimulation). Our results indicate that drNOP receptor displays mixed characteristics of both NOP and κ opioid receptors. Hence, drNOP, which has retained more of the likely ancestral features, bridges the gap between nociceptin and opiate pharmacology.
journal_name
J Mol Endocrinoljournal_title
Journal of molecular endocrinologyauthors
Rivas-Boyero AA,Herrero-Turrión MJ,Gonzalez-Nunez V,Sánchez-Simón FM,Barreto-Valer K,Rodríguez REdoi
10.1530/JME-10-0130subject
Has Abstractpub_date
2011-03-03 00:00:00pages
111-23issue
2eissn
0952-5041issn
1479-6813pii
JME-10-0130journal_volume
46pub_type
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