Effect of opioid receptor ligands on the μ-S196A knock-in and μ knockout mouse vas deferens

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Abstract

We have determined the effect of naltrexone, naloxone, [D-Ala 2,D-Leu5]enkephalin (DADLE), and morphine on the μ-S196A opioid receptor knock-in and μ-opioid receptor knockout mouse vas deferens preparations. The antagonists, naltrexone and naloxone, exhibited agonist activity and possessed IC50 values that were 14- and 37-fold greater than morphine on the S196A preparation. Morphine was found to be threefold more potent at S196A relative to wild-type μ-opioid receptor. The mouse vas deferens data suggest that S196 in transmembrane helix 4 of the μ-opioid receptor modulates efficacy. It is proposed that this may be due to decreased dimerization of the receptor. Identical IC50 values of DADLE obtained on the wild-type, S196A knock-in, and μ-opioid receptor knockout preparations support the absence of μ-δ heterodimers in the mouse vas deferens.

Original languageEnglish (US)
Pages (from-to)207-210
Number of pages4
JournalEuropean Journal of Pharmacology
Volume478
Issue number2-3
DOIs
StatePublished - Oct 8 2003

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Vas Deferens
Opioid Receptors
Knockout Mice
Ligands
Morphine
Naltrexone
Naloxone
Inhibitory Concentration 50
Dimerization

Keywords

  • Mouse
  • Opioid receptor antagonist
  • Vas deferens
  • μ-Opioid receptor knockout
  • μ-Ser196Ala

Cite this

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title = "Effect of opioid receptor ligands on the μ-S196A knock-in and μ knockout mouse vas deferens",
abstract = "We have determined the effect of naltrexone, naloxone, [D-Ala 2,D-Leu5]enkephalin (DADLE), and morphine on the μ-S196A opioid receptor knock-in and μ-opioid receptor knockout mouse vas deferens preparations. The antagonists, naltrexone and naloxone, exhibited agonist activity and possessed IC50 values that were 14- and 37-fold greater than morphine on the S196A preparation. Morphine was found to be threefold more potent at S196A relative to wild-type μ-opioid receptor. The mouse vas deferens data suggest that S196 in transmembrane helix 4 of the μ-opioid receptor modulates efficacy. It is proposed that this may be due to decreased dimerization of the receptor. Identical IC50 values of DADLE obtained on the wild-type, S196A knock-in, and μ-opioid receptor knockout preparations support the absence of μ-δ heterodimers in the mouse vas deferens.",
keywords = "Mouse, Opioid receptor antagonist, Vas deferens, μ-Opioid receptor knockout, μ-Ser196Ala",
author = "Portoghese, {Philip S} and Ping-Yee Law and Loh, {Horace H}",
year = "2003",
month = "10",
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language = "English (US)",
volume = "478",
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journal = "European Journal of Pharmacology",
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T1 - Effect of opioid receptor ligands on the μ-S196A knock-in and μ knockout mouse vas deferens

AU - Portoghese, Philip S

AU - Law, Ping-Yee

AU - Loh, Horace H

PY - 2003/10/8

Y1 - 2003/10/8

N2 - We have determined the effect of naltrexone, naloxone, [D-Ala 2,D-Leu5]enkephalin (DADLE), and morphine on the μ-S196A opioid receptor knock-in and μ-opioid receptor knockout mouse vas deferens preparations. The antagonists, naltrexone and naloxone, exhibited agonist activity and possessed IC50 values that were 14- and 37-fold greater than morphine on the S196A preparation. Morphine was found to be threefold more potent at S196A relative to wild-type μ-opioid receptor. The mouse vas deferens data suggest that S196 in transmembrane helix 4 of the μ-opioid receptor modulates efficacy. It is proposed that this may be due to decreased dimerization of the receptor. Identical IC50 values of DADLE obtained on the wild-type, S196A knock-in, and μ-opioid receptor knockout preparations support the absence of μ-δ heterodimers in the mouse vas deferens.

AB - We have determined the effect of naltrexone, naloxone, [D-Ala 2,D-Leu5]enkephalin (DADLE), and morphine on the μ-S196A opioid receptor knock-in and μ-opioid receptor knockout mouse vas deferens preparations. The antagonists, naltrexone and naloxone, exhibited agonist activity and possessed IC50 values that were 14- and 37-fold greater than morphine on the S196A preparation. Morphine was found to be threefold more potent at S196A relative to wild-type μ-opioid receptor. The mouse vas deferens data suggest that S196 in transmembrane helix 4 of the μ-opioid receptor modulates efficacy. It is proposed that this may be due to decreased dimerization of the receptor. Identical IC50 values of DADLE obtained on the wild-type, S196A knock-in, and μ-opioid receptor knockout preparations support the absence of μ-δ heterodimers in the mouse vas deferens.

KW - Mouse

KW - Opioid receptor antagonist

KW - Vas deferens

KW - μ-Opioid receptor knockout

KW - μ-Ser196Ala

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