Thermodynamic parameters of opioid binding in the presence and absence of G-protein coupling

Gabriella Fábián, S. Benyhe, J. Farkas, M. Szücs

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We have investigated the thermodynamic parameters of various opioid ligands interacting with their receptors in rat brain membranes. Affinity constants (K(a)), enthalpy and entropy values were obtained from homologous displacement experiments performed at 0, 24 and 33°C. It was found that all the opioid agonists tested ([3H]dihydromorphine (DHM) μ alkaloid; [3H]DAMGO μ peptide; [3H]deltorphin-B δ peptide) display endothermic binding accompanied with a large entropy increase, regardless of their chemical structure (alkaloid or peptide), or of their μ or δ receptor selectivity. In contrast, binding of the antagonist naloxone is exothermic, mainly enthalpy driven, Na+ or Mg2+ results only in quantitative changes of the thermodynamic parameters. In the presence of the GTP-analog Gpp(NH)p; or Gpp(NH)p + Na+; or Gpp(NH)p + Na+ + Mg2+ the affinity of DHM binding dramatically decreases which might reflect functional uncoupling of the receptor-ligand complex and G-proteins. This altered molecular interactions are also indicated by curvilinear van't Hoff plot and entropy increase. It is concluded that the thermodynamic analysis provides means of determining the underlying driving forces of ligand binding and helps to delineate its mechanism.

Original languageEnglish
Pages (from-to)151-168
Number of pages18
JournalJournal of Receptors and Signal Transduction
Volume16
Issue number3-4
Publication statusPublished - 1996

Fingerprint

Guanylyl Imidodiphosphate
Dihydromorphine
Entropy
Thermodynamics
GTP-Binding Proteins
Opioid Analgesics
Ligands
Alkaloids
Enthalpy
Ala(2)-MePhe(4)-Gly(5)-enkephalin
Peptides
Molecular interactions
Naloxone
Guanosine Triphosphate
Rats
Brain
Membranes
Experiments

Keywords

  • G-protein coupling
  • opioid binding
  • thermodynamic analysis
  • van't Hoff analysis

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Thermodynamic parameters of opioid binding in the presence and absence of G-protein coupling. / Fábián, Gabriella; Benyhe, S.; Farkas, J.; Szücs, M.

In: Journal of Receptors and Signal Transduction, Vol. 16, No. 3-4, 1996, p. 151-168.

Research output: Contribution to journalArticle

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