Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Analgesics / pharmacology
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Animals
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Brain Neoplasms / metabolism
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Chromatography, High Pressure Liquid
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Chromatography, Thin Layer
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Enkephalin, D-Penicillamine (2,5)-
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Enkephalins / pharmacology
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Humans
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Iodine / chemistry*
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Mice
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Molecular Sequence Data
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Molecular Weight
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Narcotic Antagonists / chemistry
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Narcotic Antagonists / pharmacology*
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Neuroblastoma / metabolism
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Oligopeptides / chemistry
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Oligopeptides / pharmacology*
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Receptors, Opioid, delta / agonists*
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Receptors, Opioid, delta / antagonists & inhibitors*
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Spectrometry, Mass, Fast Atom Bombardment
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Tetrahydroisoquinolines*
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Tumor Cells, Cultured
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Tyrosine / chemistry*
Substances
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Analgesics
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Enkephalins
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Narcotic Antagonists
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Oligopeptides
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Receptors, Opioid, delta
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Tetrahydroisoquinolines
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tyrosyl-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-phenylalanyl-phenylalanine
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Tyrosine
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Enkephalin, D-Penicillamine (2,5)-
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Iodine