Orphanin FQ: receptor binding and analog structure activity relationships in rat brain.
A tritiated form of orphanin FQ (a heptadecapeptide also known as Nociceptin) has been prepared. This radioligand (33 Ci/mmole) was used to develop a radioreceptor assay using rat brain homogenates. Binding was observed to be saturable, and analyses of the binding data indicate the presence of a single binding site with a dissociation constant of 5 +/- 1.1 nM and Bmax of 535 +/- 85 fmoles/mg protein. Thirty-four analogues of orphanin FQ, including a complete alanine "scan" of orphanin FQ, and truncation analogues from both the N- and C- terminals were synthesized and tested. The data obtained indicate that the N-terminus plays a more critical role in binding than the C-terminus and that residues 1, 2, 4, and 8 are essential for binding.
Dooley
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CT
Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA.
Houghten
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RA
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008969:Molecular Sequence Data; D018847:Opioid Peptides / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D013329:Structure-Activity Relationship; D000097629:Nociceptin
D018847:Opioid Peptides; D000097629:Nociceptin