Arginine residue at position 285 (R285) in the intracellular C-terminal domain of inward recti¢er potassium channel Kir2.2 is conserved in many species, but missing in previously reported human Kir2.2 sequences. We here identi¢ed the human Kir2.2 gene in normal individuals, which contained R285 in the deduced amino-acid sequence (hKir2.2/R285

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A 73-year-old Japanese man was admitted with an asymptomatic pulmonary artery aneurysm. However, chest X-ray and contrast-enhanced thoracic computed tomography revealed a protrusion at the second left branch that in fact was a pulmonary artery aneurysm with a diameter of 50 mm. Transesophageal echocardiography showed a bicuspid pulmonary valve, and cardiac catheterization revealed pulmonary stenosis with a pressure gradient of 45 mmHg, but no other heart diseases were noted. An extremely rare pulmonary artery aneurysm associated with an isolated bicuspid pulmonary valve was diagnosed.

Uric acid is generated with reactive oxygen species via xanthine oxidase (XO), and hyperuricemia, which is identified as the excess of uric acid in the blood, has been associated with vascular endothelial dysfunction. However, the effects of urate-lowering medicines on endothelial function have not been fully elucidated. Thus this study determined and compared the effects of benzbromarone (urate transporter 1 inhibitor) and febuxostat (XO inhibitor) on endothelial function. This randomized, cross-over, open-label study initially recruited 30 patients with hyperuricemia. They were divided into two groups, treated initially with benzbromarone or febuxostat for three months and then were switched for the next three months. Endothelial function was defined as reactive hyperemia indexes (RHI) determined using Endo-PAT 2000 before and at three and six months after medication using the two agents. Blood levels of asymmetric dimethylarginine (ADMA) and high-molecular-weight (HMW) adiponectin were also compared. We finally analyzed data from 24 patients whose endothelial function was assessed as described above. Our findings show that levels of uric acid significantly decreased, whereas those of HMW adiponectin and the RHI have significantly increased after treatment with benzbromarone. Meanwhile, in patients administered with febuxostat, uric acid levels tended to decrease and RHI significantly decreased. Neither of the two agents altered ADMA levels. The changes in RHI (P = 0.026) and HMW adiponectin levels (P = 0.001) were found to be significantly greater in patients treated with benzbromarone than febuxostat. Changes in the levels of HMW adiponectin and of uric acid were significantly correlated (r = −0.424, P = 0.039). Benzbromarone has increased adiponectin besides reducing uric acid levels, and thus, this might confer more benefits on endothelial function than febuxostat.

Although a potential target site of general anesthetics is primarily the GABA A receptor, a chloride ion channel, a previous study suggested that the intravenous general anesthetic propofol attenuates the M1 muscarinic acetylcholine receptor (M1 receptor)-mediated signal transduction. In the present study, we examined the target site of propofol in M1 receptor-mediated signal transduction. Two-electrode voltage-clamp method was used in Xenopus oocytes expressing both M1 receptors and associated G protein ␣ subunits (Gq␣). Propofol inhibited M1 receptor-mediated signal transduction in a dose-dependent manner (IC 50 ϭ 50 nM). Injection of guanosine 5Ј-3-O-(thio)triphosphate (GTP␥S) into oocytes overexpressing Gq␣ was used to investigate direct effects of propofol on G protein coupled with the M1 receptor. Propofol did not affect activation of Gq␣-mediated signal transduction with the intracellular injection of GTP␥S. We also studied effects of propofol on l-[N- Effects of propofol on Gs-and Gi/o-coupled signal transduction were investigated, using oocytes expressing the ␤2 adrenoceptor (␤2 receptor)/cystic fibrosis transmembrane conductance regulator or oocytes expressing the M2 muscarinic acetylcholine receptor (M2 receptor)/Kir3.1 (a member of G protein-gated inwardly rectifying K ϩ channels). Neither ␤2 receptor-mediated nor M2 receptor-mediated signal transduction was inhibited by a relatively high concentration of propofol (50 M). These results indicate that propofol inhibits M1 receptor-mediated signal transduction by selectively disrupting interaction between the receptor and associated G protein.