Loss of μ-opioid receptor-mediated G-protein activation in the pons/medulla of mice lacking the exons 2 and 3 of μ-opioid receptor gene

The G-protein activation induced by μ-opioid receptor agonists in the pons/medulla membrane obtained from mice lacking exons 2 and 3 of μ-opioid receptor gene (MOR (Exons 2 and 3)-knockout (KO) mice) was investigated by monitoring guanosine-5′-o-(3-[³⁵S]thio)triphosphate ([³⁵S]GTPγS) binding. The MOR agonists D-Ala2,MePhe4,Gly(ol)5)enkephalin, endomorphin-1 and endomorphin-2 each produced concentration-dependent increases in [³⁵S]GTPγS binding to pons/medulla membrane in wild-type mice, but not in MOR (Exons 2 and 3)-KO mice. β-Endorphin also produced a concentration-dependent increase of [³⁵S]GTPγS binding to pons/medulla membrane in wild-type mice, however the increase of [³⁵S]GTPγS binding induced by β-endorphin was partially attenuated in MOR (Exons 2 and 3)-KO mice. The present results suggest that MOR that is created from the sequences encoded with exons 2 and 3 of the MOR gene, as has been previously observed in studies of mice lacking exon 1 of this gene, may be another critical target for the activation of G-protein by MOR agonists in the mouse pons/medulla.