Region-dependent G-protein activation by μ-, δ1- and δ2-opioid receptor agonists in the brain: Comparison between the midbrain and forebrain

Abstract

The ability of selective μ- ([D-Ala 2, NHPhe 4, Gly-ol]enkephalin: DAMGO), δ 1- ([D-Pen 2, Pen 5]enkephalin: DPDPE) and δ 2- ([D-Ala 2]deltorphin II: DELT II) opioid receptor agonists to activate G-proteins in the midbrain and forebrain of mice and rats was examined by monitoring the binding of guanosine-5′- O-(3-[ 35S]thio)triphosphate ([ 35S]GTPγS). The levels of [ 35S]GTPγS binding stimulated by DAMGO in the mouse and rat midbrain were significantly greater than those by DPDPE or DELT II. However, relatively lower levels of stimulation of [ 35S]GTPγS binding by all of the agonists than would have been predicted from the receptor densities were observed in either the limbic forebrain or striatum of mice and rats. The effects of DAMGO, DPDPE and DELT II in all three regions were completely reversed by selective μ-, δ 1- and δ 2-antagonists, respectively. The results indicate that the levels of μ-, δ 1- and δ 2-opioid receptor agonist-induced G-protein activation in the midbrain are in good agreement with the previously determined distribution densities of each receptor type. Furthermore, the discrepancies observed in the forebrain might reflect differential catalytic efficiencies of receptor-G-protein coupling.