Differential effect of μ, δ, and κ ligands on G protein α subunits in cultured brain cells
- 1 September 1990
- journal article
- research article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 27 (1), 106-111
- https://doi.org/10.1002/jnr.490270116
Abstract
Rat and guinea pig fetal brain cell cultures and immunoblotting techniques were used to study the effect of receptor selective opioids on the level of the membrane‐bound α1 and α0 GTP binding protein subunits. Incubation of rat hindbrain cultures with the μ selective peptide DAGO decreased the amount of both α proteins. The reduction observed was equivalent to 36% in α0 and 41% in α1. On the other hand, incubation of rat forebrain cultures with this peptide had an opposite effect, increasing the α0 and α1 levels by 66% and 68%, respectively. This differential effect of the peptide on the G proteins at the two brain areas may reflect the selective interaction at the receptor level; DAGO induced a fast and effective receptor down‐regulation (50% decrease in Bmax) in hindbrain but not in forebrain cultures. Moreover, δ and μ selective ligands differed in their effect, as indicated by the finding that the δ selective peptide DPDPE increased the amount of both α proteins in hindbrain cultures by 40%. Similar experiments conducted with guinea pig brain aggregate cultures indicated that the κ selective agonist U50, 488 decreased the amount of the membrane bound α1 protein subunit by 56%. The results thus indicate that opioid agonists, interacting selectively with the three types of opioid receptors, induce a complex repertoire of changes in the immunoreactive levels of the membrane‐bound α GTP binding protein subunits in various CNS structures.Keywords
This publication has 43 references indexed in Scilit:
- Opioid Receptors in Magnesium‐Digitonin‐Solubilized Rat Brain Membranes Are Tightly Coupled to a Pertussis Toxin‐Sensitive Guanine Nucleotide‐Binding ProteinJournal of Neurochemistry, 1989
- G PROTEINS: TRANSDUCERS OF RECEPTOR-GENERATED SIGNALSAnnual Review of Biochemistry, 1987
- Differential ontogeny of divalent cation effects on rat brain δ-, μ-, and χ-opioid receptor bindingDevelopmental Brain Research, 1987
- Differential postnatal development of μ-, δ- and χ-opioid binding sites in rat brainDevelopmental Brain Research, 1987
- Plasticity in the phenotypic expression of brain opioid receptors: differential response of forebrain and hindbrain cultures to chemical depolarizationDevelopmental Brain Research, 1986
- Down-regulation of opiate receptors in serum-free cultures of aggregating fetal brain cellsLife Sciences, 1983
- Properties of a selective kappa agonist, U-50,488HLife Sciences, 1982
- Developmental differences between high and low affinity opiate binding sites: Their relationship to analgesia and respiratory depressionLife Sciences, 1980
- Biochemical differentiation of aggregating cell cultures of different fetal rat brain regionsBrain Research, 1977
- Morphine-like drugs inhibit the stimulation by E prostaglandins of cyclic AMP formation by rat brain homogenateNature, 1974