As a primary target for opioid drugs and peptides, the mu opioid receptor (OPRM1) plays a key role in pain perception and addiction. Genetic variants of OPRM1 have been implicated in predisposition to drug addiction, in particular the single nucleotide polymorphism A118G, leading to an N40D substitution, with an allele frequency of 10 -32%, and uncertain functions. We have measured allele-specific mRNA expression of OPRM1 in human autopsy brain tissues, using A118G as a marker. In 8 heterozygous samples measured, the A118 mRNA allele was 1.5-2.5-fold more abundant than the G118 allele. Transfection into Chinese hamster ovary cells of a cDNA representing only the coding region of OPRM1, carrying adenosine, guanosine, cytidine, and thymidine in position 118, resulted in 1.5-fold lower mRNA levels only for OPRM1-G118, and more than 10-fold lower OPRM1 protein levels, measured by Western blotting and receptor binding assay. After transfection and inhibition of transcription with actinomycin D, analysis of mRNA turnover failed to reveal differences in mRNA stability between A118 and G118 alleles, indicating a defect in transcription or mRNA maturation. These results indicate that OPRM1-G118 is a functional variant with deleterious effects on both mRNA and protein yield. Clarifying the functional relevance of polymorphisms associated with susceptibility to a complex disorder such as drug addiction provides a foundation for clinical association studies.Drug addiction is a complex disorder with a strong genetic component (1, 2). Serving as a primary target for opioid drugs and peptides, the mu opioid receptor (OPRM1) mediates the effects of morphine and heroin (3, 4). By impinging on dopaminergic pathways, OPRM1 also plays a role in addiction to other drugs of abuse, such as cocaine, nicotine, and alcohol (5, 6).Because of its central role in drug addiction, numerous studies have addressed potential contributions of polymorphisms in the gene encoding OPRM1 to addiction susceptibility (7,8). Among multiple single nucleotide polymorphisms (SNPs) 2 in OPRM1, C17T (A6V), and A118G (N40D) are well studied nonsynonymous SNPs located at the N terminus of the receptor. In particular, A118G, with an allele frequency of 10 -32% in different ethnic groups (9), has been associated with susceptibility to heroin, nicotine, and alcohol addiction (10 -12). However, other studies have failed to corroborate these associations (13, 14), possibly as a result of population admixture.The A118G polymorphism has also been linked to differences in pharmacological properties of OPRM1. In a Swedish population, the G118 variant was shown to correlate with poor response to naltrexone in the treatment of alcoholism (15). Moreover, OPRM1-antagonist naloxone elicited an increased cortisol response in individuals with a G118 allele (16,17). In transfected cells, OPRM1-Asp 40 was reported to have 3-fold higher affinity for ␤-endorphin than OPRM1-Asn 40 (18), suggesting a gain of function, but subsequent studies have failed to corroborate these results...

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Five new, discretely sized, magic-size II–VI nanoclusters are synthesized in primary-amine bilayer templates and are isolated as the derivatives [(CdS)34(n-butylamine)18], [(ZnS)34(n-butylamine)34], [(ZnSe)13(n-butylamine)13], [(CdTe)13(n-propylamine)13], and [(ZnTe)13(n-butylamine)13]. The nanoclusters are characterized by elemental analysis, UV–visible absorption spectroscopy, laser-desorption-ionization mass spectrometry, and transmission electron microscopy. Four of the nanocluster precursors are converted to wurtzitic CdS, ZnS, and ZnSe quantum platelets and CdTe quantum belts, respectively, under mild conditions.

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