1 The goal of this study was to characterize the agonist pharmacology of human 5-HT 2A , 5-HT 2B and 5-HT 2C (VSV) receptors expressed in CHO-K1 (Chinese hamster ovary) cells. 2 We used a¯uorometric imaging plate reader (FLIPR) which allows rapid detection of rises in intracellular calcium levels upon the addition of agonists. 5 Many agonists tested had partial agonist actions when compared to 5-HT, and a wide range of relative e cacies were exhibited, which was cell line dependent. For example, mCPP had a relative e cacy of 65% at 5-HT 2C receptors but 525% at either 5-HT 2A or 5-HT 2B receptors. 6 Interpretation of literature values of functional assays using di erent cell lines, di erent receptor expression levels and di erent receptor isoforms, is complex. Species di erences and the previous use of antagonist radioligands to characterize agonist potency in binding assays emphasizes the importance of studying agonists in the same experiment using the same assay conditions and parental cell lines.

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The possibility of gene interactions in Alzheimer's disease (AD) has been suggested by the finding of an association of the AA genotype of the alpha-1 antichymotrypsin (AACT) gene and the apolipoprotein E (apoE) epsilon 4/4 genotype in AD. We tested this possibility by genotyping a large series of clinically and neuropathologically confirmed cases of AD and a series of cases with dementia with Lewy bodies (DLB) with a matched control group for the AACT locus and apoE. ApoE genotyping showed the established finding of an increased frequency of the apoE epsilon 4 allele in AD and in DLB. The AD and DLB groups differed between each other with a higher epsilon 2 allele frequency and a reduced incidence of the epsilon 4/4 genotype in DLB. Differences in the apoE frequencies may account for some of the differences between the two diseases. No association was found for the AACT A allele in AD or DLB in the groups as a whole or when stratified with respect to apoE, with the exception of a trend showing an increased incidence of the apoE epsilon 4/4 AACT AA genotype combination in AD patients (chi 2 = 3.18, p = 0.07), although in DLB this was not apparent (chi 2 = 0.0, p = 1.0). The AACT A allele is not a major risk factor for late-onset AD or DLB.

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