COMT Val108/158Met genotype affects the mu-opioid receptor system in the human brain: Evidence from ligand-binding, G-protein activation and preproenkephalin mRNA expression

As a mechanism how COMT might exert its action on MOP receptors, it has been suggested that at least in striatopallidal circuits COMT Val108/158Met impacts on enkephalin, which is capable of reciprocally regulating MOP receptor expression. Thus, we assessed preproenkephalin mRNA by in situ hybridization. In the striatum, mRNA levels were significantly higher in COMT Met108/158 homozygous cases indicating that MOP binding sites and enkephalin are regulated in parallel. Moreover, the transcript was not detectable in the thalamus. Thus, mechanisms other than an enkephalin-dependent receptor turnover must be responsible for COMT-related differences in MOP binding site availability in the human brain.