Thermodynamic analysis of the temperature dependence of the dissociation constant of naloxone at opioid delta receptors in the mouse isolated vas deferens

R. B. Raffa, K. D. Wild, H. I. Mosberg, Frank Porreca

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Abstract

Dissociation constants (K(B)) for naloxone inhibition of the actions of DPDPE in the mouse isolated vas deferens preparation (inhibition of electrically induced twitch) were determined at five temperatures ranging between 25 and 40°C. The values of K(B) tended to increase with temperature over the range examined, indicating that the affinity of naloxone for the opioid δ receptor is an inverse function of temperature. Using these data, the thermodynamic quantities ΔG°' (change in free energy), ΔH°' (change in enthalpy) and ΔS°' (change in entropy) were calculated from a van't Hoff plot of In (K(B)) against 1/T. The thermodynamic quantities determined in this study in vivo (ΔG°' = -10.59 kcal mol-1, ΔH°' = -15.73 kcal mol- 1 and ΔS°' = -0.0168 kcal mol-1 °K-1) are consistent with data reported from radioligand binding studies in vitro and suggest that the interaction between naloxone and the opioid δ receptor in the mouse isolated vas deferens is enthalpy driven. These data represent the first evaluation of the thermodynamics of opioid antagonist/receptor interaction in a physiological assay.

Original languageEnglish (US)
Pages (from-to)1030-1035
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume263
Issue number3
StatePublished - 1992

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delta Opioid Receptor
Vas Deferens
Naloxone
Thermodynamics
Opioid Receptors
Temperature
D-Penicillamine (2,5)-Enkephalin
Narcotic Antagonists
Entropy
naloxone receptor

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Thermodynamic analysis of the temperature dependence of the dissociation constant of naloxone at opioid delta receptors in the mouse isolated vas deferens",
abstract = "Dissociation constants (K(B)) for naloxone inhibition of the actions of DPDPE in the mouse isolated vas deferens preparation (inhibition of electrically induced twitch) were determined at five temperatures ranging between 25 and 40°C. The values of K(B) tended to increase with temperature over the range examined, indicating that the affinity of naloxone for the opioid δ receptor is an inverse function of temperature. Using these data, the thermodynamic quantities ΔG°' (change in free energy), ΔH°' (change in enthalpy) and ΔS°' (change in entropy) were calculated from a van't Hoff plot of In (K(B)) against 1/T. The thermodynamic quantities determined in this study in vivo (ΔG°' = -10.59 kcal mol-1, ΔH°' = -15.73 kcal mol- 1 and ΔS°' = -0.0168 kcal mol-1 °K-1) are consistent with data reported from radioligand binding studies in vitro and suggest that the interaction between naloxone and the opioid δ receptor in the mouse isolated vas deferens is enthalpy driven. These data represent the first evaluation of the thermodynamics of opioid antagonist/receptor interaction in a physiological assay.",
author = "Raffa, {R. B.} and Wild, {K. D.} and Mosberg, {H. I.} and Frank Porreca",
year = "1992",
language = "English (US)",
volume = "263",
pages = "1030--1035",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
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T1 - Thermodynamic analysis of the temperature dependence of the dissociation constant of naloxone at opioid delta receptors in the mouse isolated vas deferens

AU - Raffa, R. B.

AU - Wild, K. D.

AU - Mosberg, H. I.

AU - Porreca, Frank

PY - 1992

Y1 - 1992

N2 - Dissociation constants (K(B)) for naloxone inhibition of the actions of DPDPE in the mouse isolated vas deferens preparation (inhibition of electrically induced twitch) were determined at five temperatures ranging between 25 and 40°C. The values of K(B) tended to increase with temperature over the range examined, indicating that the affinity of naloxone for the opioid δ receptor is an inverse function of temperature. Using these data, the thermodynamic quantities ΔG°' (change in free energy), ΔH°' (change in enthalpy) and ΔS°' (change in entropy) were calculated from a van't Hoff plot of In (K(B)) against 1/T. The thermodynamic quantities determined in this study in vivo (ΔG°' = -10.59 kcal mol-1, ΔH°' = -15.73 kcal mol- 1 and ΔS°' = -0.0168 kcal mol-1 °K-1) are consistent with data reported from radioligand binding studies in vitro and suggest that the interaction between naloxone and the opioid δ receptor in the mouse isolated vas deferens is enthalpy driven. These data represent the first evaluation of the thermodynamics of opioid antagonist/receptor interaction in a physiological assay.

AB - Dissociation constants (K(B)) for naloxone inhibition of the actions of DPDPE in the mouse isolated vas deferens preparation (inhibition of electrically induced twitch) were determined at five temperatures ranging between 25 and 40°C. The values of K(B) tended to increase with temperature over the range examined, indicating that the affinity of naloxone for the opioid δ receptor is an inverse function of temperature. Using these data, the thermodynamic quantities ΔG°' (change in free energy), ΔH°' (change in enthalpy) and ΔS°' (change in entropy) were calculated from a van't Hoff plot of In (K(B)) against 1/T. The thermodynamic quantities determined in this study in vivo (ΔG°' = -10.59 kcal mol-1, ΔH°' = -15.73 kcal mol- 1 and ΔS°' = -0.0168 kcal mol-1 °K-1) are consistent with data reported from radioligand binding studies in vitro and suggest that the interaction between naloxone and the opioid δ receptor in the mouse isolated vas deferens is enthalpy driven. These data represent the first evaluation of the thermodynamics of opioid antagonist/receptor interaction in a physiological assay.

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