PROSTAGLANDIN E(2) INDUCES UP-REGULATION OF MURINE MACROPHAGE BETA-ENDORPHIN RECEPTORS

Cultured murine bone marrow macrophages specifically bound I-125-label ed beta-endorphin. Binding was displaceable by 100 times molar excess of full-length beta-endorphin but was insensitive to the opioid recept or antagonist, naloxone. Binding was inhibited by beta-endorphin's C-t erminal tetrapeptide, lys-lys-gly-glu, but not by the truncated N-term inal 27 amino acid fragment, indicating that binding of beta-endorphin to this receptor is dependent on its C-terminus. Macrophages incubate d for 24 h with 10(-8)-10(-5) M prostaglandin E(2) showed a dose-depen dent increase in beta-endorphin binding, implying receptor up-regulati on. This was also observed in response to the phosphodiesterase inhibi tor, isobutylmethylxanthine, indicating that regulation of these recep tors may be mediated through a cAMP-dependent process. This is the fir st demonstration that beta-endorphin receptor expression can be positi vely regulated.