Endomorphin‐Stimulated [³⁵S]GTPγS Binding in Rat Brain: Evidence for Partial Agonist Activity at μ‐Opioid Receptors

Abstract

Abstract:Endomorphin-1 is a peptide whose binding selectivity suggests a role as an endogenous ligand at ‚u-opioid receptors. In the present study, the effect of endomorphin-1 on ‚u receptor-coupled G proteins was compared with that of the~agonist DAMGO by using agonist-stimulated These results demonstrate that endomorphin-1 is a partial agonist for G protein activation at the~s-opioid receptor in brain.

Endomorphin-2: A Biased Agonist at the μ-Opioid Receptor

“…The endomorphins were reported to be partial agonists at MOPr in some cases, such as in GTP␥S binding assays with spinal cord and thalamus (Hosohata et al, 1998;Narita et al, 1998;Sim et al, 1998;Xie et al, 2008) and in inhibition of neuronal Ca 2ϩ currents (Connor et al, 1999), whereas the endomorphins behaved as full agonists in other cases, such as inhibition of contraction of mouse vas deferens (Al-Khrasani et al, 2001;Rónai et al, 2006); such differences are likely to depend in part on the receptor reserve in each tissue. In the present study with LC neurons, we found endomorphin-2 to be a full agonist for activation of GIRK current.…”

“…35 S]GTP␥S binding assays revealed the endomorphins to have low efficacy values close to those of morphine (Hosohata et al, 1998;Narita et al, 1998;Sim et al, 1998;Xie et al, 2008) but the endomorphins were able to induce efficient trafficking of MOPr under conditions where morphine was ineffective (Burford et al, 1998;McConalogue et al, 1999;Trafton et al, 2000). The advantages of quantifying efficacy with full concentration-response curves and of examining occupancy-response relationships are that such differences can be observed more clearly and can be quantified.…”

The Endomorphin System and Its Evolving Neurophysiological Role

“…35 S]guanosine 5Ј-O-(3-thio)triphosphate binding through the -opioid receptors in rat thalamus membrane preparations (Kakizawa et al, 1998;Sim et al, 1998;Fichna et al, 2006a), in the PAG , and in the pons/medulla of -opioid receptornondeficient mice . Both peptides were potent -opioid receptor agonists in the aequorin luminescence-based calcium assay performed on recombinant Chinese hamster ovary cell lines (Fichna et al, THE ENDOMORPHIN SYSTEM AND ITS NEUROPHYSIOLOGICAL ROLE TABLE 2 …”

“…2006b). The autoradiographic methods showed that in the CNS endomorphins labeled the same binding sites as DAMGO, a classic -opioid receptor-selective ligand (Goldberg et al, 1998;Kakizawa et al, 1998;Sim et al, 1998). Results of the in vivo studies also demonstrated that endomorphins are -opioid receptor ligands.…”

“…Endomorphin-1 and endomorphin-2 are regarded as partial agonists of -opioid receptors. The efficacy of endomorphins in many bioassays, such as guanosine 5Ј-O-(3-thio)triphosphate binding, is slightly lower than that of DAMGO but higher than that of morphine (Alt et al, 1998;Harrison et al, 1998;Sim et al, 1998). The extent to which these relative efficacies apply to the biological activity of endomorphins has yet to be elucidated.…”