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

Philip S. Portoghese; Ping Yee Law; Horace H. Loh

doi:10.1016/j.ejphar.2003.08.041

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

Philip S. Portoghese, Ping Yee Law, Horace H. Loh

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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 language	English (US)
Pages (from-to)	207-210
Number of pages	4
Journal	European Journal of Pharmacology
Volume	478
Issue number	2-3
DOIs	https://doi.org/10.1016/j.ejphar.2003.08.041
State	Published - Oct 8 2003

Bibliographical note

Funding Information:
We thank Mary Lunzer for conducting the mouse vas deferens experiments. This research was supported by NIH research grants DA01533 (PSP), DA07339, DA0564, DA11806, KO5-DA70554 (HHL) and KO5-DA-00513 (PYL).

Keywords

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

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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.",

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note = "Funding Information: We thank Mary Lunzer for conducting the mouse vas deferens experiments. This research was supported by NIH research grants DA01533 (PSP), DA07339, DA0564, DA11806, KO5-DA70554 (HHL) and KO5-DA-00513 (PYL).",

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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.

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

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