Introduction. Phospholipase A 2 (PLA 2 ) is a group of lipolytic enzymes that catalyze the hydrolysis of fatty acid ester bonds at the sn-2 position of phospholipids. This enzyme is thought to play an important role in the biosynthesis of eicosanoids via the release of arachidonic acid from biomembranes. Another product from biomembranes, a lysophospholipid, is converted to plateletactivating factor (PAF) known as an inflammatory mediator. PLA 2 s have been generally classified into secretory PLA 2 (sPLA 2 ), cytosolic PLA 2 (cPLA 2 ), and Ca 2+ -independent PLA 2 (iPLA 2 ) by their molecular weights, amino acid sequences, and calcium requirements. 1 cPLA 2 comprises three distinct types of enzymes: R, β, and γ. 2 cPLA 2 R, an 85-kDa protein, contains a calcium-dependent lipid binding domain and a catalytic domain, requires micromolar levels of Ca 2+ for membrane translocation, and has a specificity for arachidonic acid bound to the sn-2 position of phospholipids 3 in contrast with sPLA 2 and iPLA 2 which have broad substrate specificities, suggesting that cPLA 2 R is involved in the production of eicosanoids.
To study the molecular mechanism how cortical areas are specialized in adult primates, we searched for area-specific genes in macaque monkeys and found striking enrichment of serotonin (5-hydroxytryptamine, 5-HT) 1B receptor mRNA, and to a lesser extent, of 5-HT2A receptor mRNA, in the primary visual area (V1). In situ hybridization analyses revealed that both mRNA species were highly concentrated in the geniculorecipient layers IVA and IVC, where they were coexpressed in the same neurons. Monocular inactivation by tetrodotoxin injection resulted in a strong and rapid (<3 h) downregulation of these mRNAs, suggesting the retinal activity dependency of their expression. Consistent with the high expression level in V1, clear modulatory effects of 5-HT1B and 5-HT2A receptor agonists on the responses of V1 neurons were observed in in vivo electrophysiological experiments. The modulatory effect of the 5-HT1B agonist was dependent on the firing rate of the recorded neurons: The effect tended to be facilitative for neurons with a high firing rate, and suppressive for those with a low firing rate. The 5-HT2A agonist showed opposite effects. These results suggest that this serotonergic system controls the visual response in V1 for optimization of information processing toward the incoming visual inputs.
Genetic factors have been implicated in playing a significant role in susceptibility to anorexia nervosa (AN). Among many candidate genes for AN, an association with the A allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A receptor has been reported. However, these findings are controversial and all patients studied to date have been Caucasian. This study was designed to determine whether this association is reproducible in Japanese subjects. This case-control study of a cohort of 75 female Japanese AN sufferers and 127 normal female control subjects revealed no significant association between the 5-HT2A promoter polymorphism and AN. Thus, at least for Japanese subjects, the A-allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A receptor gene does not contribute to a predisposition to AN.
A highly efficient and practical synthetic method for the preparation of pyrone diesters was established. The pyrone diester 3c can be prepared from readily available starting materials on a multihundred gram scale. The pyrone diester 3c can easily be converted to dolutegravir sodium (1). The synthetic route demonstrated herein provides an efficient and atomeconomical synthetic method for preparing this potent anti-HIV agent.
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