The human µ opioid receptor gene: 5´ regulatory and intronic sequences

Abstract

The human µ opioid receptor (hMOR) interacts with endogenous and exogenous ligands to mediate its characteristic effects, reward, dependence, and analgesia. Specifically binding morphine, it represents the target of the most valuable pain killer in contemporary medicine. Analysis of its structure, regulation, and expression will elucidate molecular processes involved in opioid/morphine-induced actions. Thus we have contributed significant information on the genomic organization of hMOR, extending the previously known cDNA sequence information (2162 bp) up to a total of 6968 bp: we have determined 2412 bp of 5´ regulatory region, identified one major and three minor transcription initiation sites 216, 285, 358, and 373 bp upstream from the translation start codon, as well as potential binding sites for transcriptional regulatory factors, including putative cis-acting enhancer motifs for a glucocorticoid response element, cAMP response elements, activator proteins 1, and Yin Yang-1 boxes. Moreover, we have analyzed the 5´ and 3´ nucleotide sequences of introns 1 and 3 and the complete sequence of intron 2. In addition to the classical consensus sequences involved in RNA splicing, we have identified intronic repeats (^A/_TGGG) found to regulate alternative splicing, mutations of which cause human disease. A similar genetic variant is observed in the hMOR gene. Taken together, the sequence information presented will allow comprehensive analysis of this gene for allelic variations associated with vulnerability to drug abuse or individual differences in opiate mediated analgesia.