Selectivity in the control of opiate receptor density in the animal and in cultured fetal brain cells.

Two aspects of the mechanisms controlling down-regulation of opiate receptors were studied: 1. The possibility that morphine does not induce down-regulation of delta receptors is an observation confined to in vitro conditions was investigated by studying the regulation of receptors in neuroblastoma-glioma cells in diffusion chambers implanted in ICR mice peritonea. Injection of morphine for 9 days at a dose inducing opiate tolerance did not change the number of receptors in the chamber-implanted cells, whereas etorphine at a 1/100 dose had a profound effect. 2. Embryonic cells from rat forebrain or hindbrain were cultured with mu type opiate alkaloid (morphine) or peptide (morphiceptin) to further establish the selectivity of opiate action. A partial effect of morphiceptin but not morphine on the number of receptors in hindbrain aggregates was observed. Thus, conclusions derived from experiments with morphine may not be applicable to mu type peptides. The results suggest that the mammalian brain may contain sub-types of mu receptors. Alternatively, although interacting with a common mu receptor, morphine and mu opioid peptides may induce different regulatory mechanisms.