Expression of calcitonin gene-related peptide receptor subunits in cultured neurons following morphine treatment

Calcitonin gene-related peptide (CGRP) has been implicated in pain transmission and morphine tolerance. Although the release of CGRP is well observed in pain-related regions after chronic morphine treatment, a lack of evidence is obvious for the expression of CGRP-receptor subunits, calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1) in the brain. In this study, we investigated in vitro the time-course of the expression of CRLR and RAMP1 following morphine administration, and compared their changes among striatal, cerebellar, cortical and the spinal cord neurons. The levels of CRLR showed no significant changes in striatal cultures during morphine treatment, while the levels of RAMP1 time-dependently increased. Decrease in the content of RAMP1 was detected in cerebellar cultures. Apart from these facts, no significant changes of CRLR or RAMP1 were detected in any other cultures. The changes in the level of CRLR on the cell membrane were examined. Significant increases of surface CRLR were detected in both striatal and cerebellar neurons after morphine treatment, while cortical neurons not. It is concluded that the expression of gross and surface CRLR and RAMP1 were differentially regulated in primary neuronal cultures following morphine treatments, indicating the involvement of CGRP receptor in morphine associated functions.