Prostaglandin E2 induces up-regulation of murine macrophage beta-endorphin receptors

Cultured murine bone marrow macrophages specifically bound 125I-labeled beta-endorphin. Binding was displaceable by 100 times molar excess of full-length beta-endorphin but was insensitive to the opioid receptor antagonist, naloxone. Binding was inhibited by beta-endorphin's C-terminal tetrapeptide, lys-lys-gly-glu, but not by the truncated N-terminal 27 amino acid fragment, indicating that binding of beta-endorphin to this receptor is dependent on its C-terminus. Macrophages incubated for 24 h with 10(-8)-10(-5) M prostaglandin E2 showed a dose-dependent increase in beta-endorphin binding, implying receptor up-regulation. This was also observed in response to the phosphodiesterase inhibitor, isobutylmethylxanthine, indicating that regulation of these receptors may be mediated through a cAMP-dependent process. This is the first demonstration that beta-endorphin receptor expression can be positively regulated.