Endomorphin-stimulated [35S]GTPgammaS binding in rat brain: evidence for partial agonist activity at mu-opioid receptors

J Neurochem. 1998 Apr;70(4):1567-76. doi: 10.1046/j.1471-4159.1998.70041567.x.


Endomorphin-1 is a peptide whose binding selectivity suggests a role as an endogenous ligand at mu-opioid receptors. In the present study, the effect of endomorphin-1 on mu receptor-coupled G proteins was compared with that of the mu agonist DAMGO by using agonist-stimulated [35S]GTPgammaS binding in rat brain. [35S]GTPgammaS autoradiography revealed a similar localization of endomorphin-1- and DAMGO-stimulated [35S]GTPgammaS binding in areas including thalamus, caudate-putamen, amygdala, periaqueductal gray, parabrachial nucleus, and nucleus tractus solitarius. Naloxone blocked endomorphin-1-stimulated labeling in all regions examined. Although the distribution of endomorphin-1-stimulated [35S]GTPgammaS binding resembled that of DAMGO, the magnitude of endomorphin-1-stimulated binding was significantly lower than that produced by DAMGO. Concentration-effect curves of endomorphin-1 and DAMGO in thalamic membranes confirmed that endomorphin-1 produced only 70% of DAMGO-stimulated [35S]GTPgammaS binding. Differences in maximal stimulation of [35S]GTPgammaS binding between DAMGO and endomorphin-1 were magnified by increasing GDP concentrations, and saturation analysis of net endomorphin-1-stimulated [35S]GTPgammaS binding revealed a lower apparent Bmax value than that obtained with DAMGO. Endomorphin-1 also partially antagonized DAMGO stimulation of [35S]GTPgammaS binding. These results demonstrate that endomorphin-1 is a partial agonist for G protein activation at the mu-opioid receptor in brain.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoradiography
  • Brain / metabolism*
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalins / pharmacology
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism*
  • Guanosine Diphosphate / pharmacology
  • Male
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Oligopeptides / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, mu / agonists*
  • Sulfur Radioisotopes


  • Enkephalins
  • Narcotic Antagonists
  • Oligopeptides
  • Receptors, Opioid, mu
  • Sulfur Radioisotopes
  • endomorphin 1
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Guanosine Diphosphate
  • Naloxone
  • Guanosine 5'-O-(3-Thiotriphosphate)