Structure, tissue distribution, and pharmacological characterization of Xenopus orexins.
We isolated the Xenopus gene encoding prepro-orexin to predict the structures of orexins in submammalian chordates. Putative mature Xenopus orexin-A and -B are highly similar to each mammalian counterpart. Especially, the C-terminal 10 residues were highly conserved among these species and isopeptides. Immunohistochemical examination of Xenopus brain revealed that orexin-containing neurons were highly specifically localized in the ventral hypothalamic nucleus. A rich network of immunoreactive fibers was found in various regions of the Xenopus brain. The distribution was similar to that of mammalian orexins. Xenopus orexin-A and -B specifically bind and activate human orexin receptors expressed in Chinese hamster ovary cells. Of interest, Xenopus orexin-B had several-fold higher affinity to human OX2R compared with human orexins. These results suggest that Xenopus orexin-B might be a useful pharmacological tool as an OX2R selective high-affinity agonist.
Shibahara
M
M
Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
Sakurai
T
T
Nambu
T
T
Takenouchi
T
T
Iwaasa
H
H
Egashira
S I
SI
Ihara
M
M
Goto
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016466:CHO Cells; D002352:Carrier Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014018:Tissue Distribution; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; C000596229:HCRT protein, human; C578626:HCRTR2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide