Tyrosine-iodination converts the delta-opioid peptide antagonist TIPP to an agonist.
The binding properties and pharmacological activities of H-Tyr(3'-I)-Tic-Phe-Phe-OH ([Tyr(3'-I)1]TIPP) were studied. Similar to the delta-opioid receptor antagonist H-Tyr-Tic-Phe-Phe-OH (TIPP), [Tyr(3'-I)1]TIPP is a selective and potent ligand at delta-opioid receptors. The displacement curve of [3H]diprenorphine binding by [Tyr(3'-I)1]TIPP was shifted to the right in the presence of Na+ and 5'-guanylylimidodiphosphate, suggesting that it acted as a delta-opioid receptor agonist. [Tyr(3'-I)1]TIPP also behaved as a full agonist in the mouse vas deferens assay and its effect was both naloxone- and TIPP-reversible. These data show that monoiodination at the 3'-position of the N-terminal tyrosine aromatic ring of TIPP converted it from a potent and selective antagonist to a full agonist at delta-opioid receptors.
Lee
P H
PH
Division of Cell Biology, Burroughs Wellcome Co., Research Triangle Park, NC 27709, USA.
Nguyen
T M
TM
Chung
N N
NN
Schiller
P W
PW
Chang
K J
KJ
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D006801:Humans; D007455:Iodine / Q000737:chemistry*; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009292:Narcotic Antagonists / Q000737:chemistry / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000037:antagonists & inhibitors*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D044005:Tetrahydroisoquinolines; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000737:chemistry*
D000700:Analgesics; D004745:Enkephalins; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D044005:Tetrahydroisoquinolines; C082263:tyrosyl-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-phenylalanyl-phenylalanine; D014443:Tyrosine; D020881:Enkephalin, D-Penicillamine (2,5)-; D007455:Iodine