Anti-ADRA1A monoclonal antibody, clone FQS0702(C)

There is large interindividual variability and ethnic differences in phenylephrine-mediated vasoconstriction. We tested the hypothesis that genetic variation in ADRA1A, the alpha(1A) adrenergic receptor gene, contributes to the variability and ethnic differences. We measured local dorsal hand vein responses to increasing doses of phenylephrine in 64 Caucasians and 42 African-Americans and genotyped for 32 ADRA1A single nucleotide polymorphisms. The ED50 ranged from 11 to 5442 ng min(-1), and the E-max ranged from 13.5-100%. The rs574647 variant was associated with a trend towards lower logED(50) in each race and in the combined cohort (P = 0.008). In addition, rs1079078 was associated with a trend to higher logED50 in each race and in the combined cohort (P = 0.011). Neither variant accounted for the ethnic differences in response. None of the ADRA1A haplotypes was associated with the outcomes. In conclusion, ADRA1A variants do not contribute substantially to the marked interindividual variability or ethnic differences in phenylephrine-mediated venoconstriction.

Various sleep abnormalities, such as delayed sleep onset, frequent awakening and daytime sleepiness, deteriorate the quality of life in patients with chronic kidney disease (CKD), including those on haemodialysis (HD). Although there are some candidate causative molecules in the central nervous system, the contribution of peripheral blood cells (PBCs) remains unclear. In this study, we performed polysomnographic analysis in CKD patients and used PBCs to examine the expression of genes related to sleep and wakefulness states. Polysomnographic analysis was performed in 9 CKD patients and 6 controls. Genes related to sleep and wakefulness were evaluated by RNA microarray in 19 subjects, including CKD patients and control subjects. Polysomnographic analysis revealed that the duration of the rapid eye movement (REM)/non-REM phases during total sleep time was different between CKD patients and healthy controls. In mRNA microarray evaluation, hierarchical clustering analysis showed different patterns of sleep-related gene expression in HD patients. mRNA expression levels of GABA receptor (GABBR2), noradrenaline receptor (ADRA1A), dopamine receptor (DRD1) and histamine receptor (HRH1) showed an inverse correlation with renal function. Moreover, the mRNA expression of orexin and its receptor (HCRTR1 and HCRTR2) was also inversely correlated with renal function. These data indicate that the expression of sleep-related genes in PBCs of CKD patients may be associated with sleep abnormalities.