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Biomedical subjects

M Odagiri

Publications and source records attributed to M Odagiri.

10 recordsLinked to original sources
PubMed1999

RGS7 and RGS8 differentially accelerate G protein-mediated modulation of K+ currents.

The recently discovered family of RGS (regulators of G protein signaling) proteins acts as GTPase activating proteins which bind to alpha subunits of heterotrimeric G proteins. We previously showed that a brain-specific RGS, RGS8 speeds up the activation and deactivation kinetics of the G protein-coupled inward rectifier K+ channel (GIRK) upon receptor stimulation (Saitoh, O., Kubo, Y., Miyatani, Y., Asano, T., and Nakata, H. (1997) Nature 390, 525-529). Here we report the isolation of a full-length rat cDNA of another brain-specific RGS, RGS7. In situ hybridization study revealed that RGS7 mRNA is predominantly expressed in Golgi cells within granule cell layer of cerebellar cortex. We observed that RGS7 recombinant protein binds preferentially to Galphao, Galphai3, and Galphaz. When co-expressed with GIRK1/2 in Xenopus oocytes, RGS7 and RGS8 differentially accelerate G protein-mediated modulation of GIRK. RGS7 clearly accelerated activation of GIRK current similarly with RGS8 but the acceleration effect of deactivation was significantly weaker than that of RGS8. These acceleration properties of RGS proteins may play important roles in the rapid regulation of neuronal excitability and the cellular responses to short-lived stimulations.

Amino Acid Sequence↗
PubMed1999

Protective effect of a vasopressin-1 selective antagonist, OPC-21268, against ethanol-induced damage of the rat gastric wall.

Since endogenous vasopressin has been reported to be an aggressor in the gastric mucosa and a vasoconstrictor in the gastric circulation, we investigated the gastric cytoprotective effects of OPC-21268, a newly developed, nonpeptide, orally active vasopressin-1 receptor antagonist, on ethanol-induced gastric injury in rats. The rats were treated with OPC-21268 or placebo 2 hr before ethanol administration, and the gastric mucosa was evaluated macroscopically for ulcer damage, and histologically for gastric mucosal injury. Gastric mucosal blood flow, erythrocyte volume, and erythrocyte velocity were also measured in groups given saline, ethanol alone, and ethanol after OPC-21268. To investigate the role of systemic or locally secreted vasopressin, we measured plasma and tissue (gastric mucosa) vasopressin concentrations after ethanol or vehicle administration. Prophylactic OPC-21268 treatment improved the gastric ulcer score in a dose-dependent manner, and histological examination demonstrated that the drug significantly ameliorated the gastric injury induced by ethanol. The hemodynamic values obtained in the OPC-21268-treated and ethanol-treated group were similar to those in the saline control group, but values were significantly (P < 0.05) higher for gastric mucosal blood flow and erythrocyte velocity and lower for erythrocyte volume compared to the group given ethanol alone. Plasma vasopressin concentrations were not significantly different in the control group and at 15, 30, and 60 min after administration of ethanol. However, ethanol administration caused a threefold increase in gastric tissue vasopressin level (P < 0.05) compared to the control group. These results suggested that OPC-21268 relieved congestive hyperemia in the gastric mucosa and ameliorated the mucosal injury caused by ethanol, probably as a result of inhibition of vasopressin-mediated actions on the stomach. The vasopressin involved was probably generated locally in the gastric mucosa after ethanol administration.

Animals↗
PubMed1994

Renal and hormonal responses to repeated treatment with enalapril in non-azotemic cirrhosis with ascites.

Since a single dose of the angiotensin-converting enzyme inhibitor enalapril was shown to cause natriuresis in cirrhosis in a previous study, we investigated whether repeated doses of this substance would sustain a favorable renal effect in cirrhosis. Ten milligrams of enalapril maleate were administered once a day for 8 days to ten patients with non-azotemic cirrhosis and ascites. Enalapril reduced blood pressure significantly at 4 to 12 h (systolic blood pressure) and 2, 6, and 8 h (diastolic blood pressure) on day 2, compared to pretreatment (day 0) values, but this depressor effect decreased on day 8. No change in heart rate could be detected. Enalapril significantly suppressed serum angiotensin-converting enzyme activity and plasma aldosterone concentration (p < 0.001 to 0.01), which were elevated prior to treatment, with pretreatment values of 25.8 +/- 1.8 IU/l for serum angiotensin-converting enzyme activity and 241 +/- 67 pg/ml for plasma aldosterone concentration. This drug caused a 12 to 24% increase (p < 0.05 to 0.01) in mean daily urinary volume and a 40 to 54% increase (p < 0.001 to 0.01) in mean daily urinary sodium excretion from the respective pretreatment baselines during the 8-day period. Creatinine clearance was improved (p < 0.05) by the treatment, with mean improvement values from 24 to 34% above the pretreatment value of 47.4 +/- 4.3 ml/min.(ABSTRACT TRUNCATED AT 250 WORDS)

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