Hitoshi Maegawa

Specific binding of atrial natriuretic polypeptide to renal basolateral membranes in spontaneously hypertensive rats (SHR) and stroke-prone SHR

The binding of alpha-human atrial natriuretic polypeptide (alpha-hANP) to basolateral membranes isolated from renal cortex of spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHR-SP) was measured at 0 degree C and compared with that of Wistar-Kyoto rats (WKY). The binding of 125I-alpha-hANP in SHR and SHR-SP at 14-15 weeks old demonstrated different binding profiles compared with that in WKY, though there were no apparent differences of the profiles among WKY, SHR and SHR-SP at 5 weeks old. For the high affinity binding sites, the apparent dissociation constant and the maximal binding capacity in SHR and SHR-SP were significantly decreased in comparison with those in WKY. The present data suggest that the altered characteristics of specific receptors for atrial natriuretic polypeptide in SHR and SHR-SP may be involved in the development or maintenance of genetic hypertension.

Intestinal absorption of cephalosporin antibiotics: correlation between intestinal absorption and brush-border membrane transport

Abstract— The absorption of seven cephalosporin antibiotics from the in‐situ intestinal loop at pH 7.4 and their transport by brush‐border membrane vesicles in the presence of an inward H+ gradient ([pH]i = 7.5, [pH]o = 6.0) were examined. A good correlation was found between the intestinal absorption rate and the initial uptake rate by brush‐border membrane vesicles. The data suggest that the transport study using intestinal brush‐border membrane vesicles is useful as a model system for the intestinal absorption of β‐lactam antibiotics.

Inhibition of the activation of hepatic stellate cells by arundic acid via the induction of cytoglobin

BACKGROUND The activation of hepatic stellate cells plays a central role in the development of liver fibrosis during chronic liver trauma. The aim of the present study was to identify a compound that inhibits the activation process of stellate cells. METHODS Rat primary cultured stellate cells and a human stellate cell line (LX-2) were used. The effects of arundic acid on the expression of α-smooth muscle actin, collagen 1α1, and cytoglobin were evaluated. RESULTS Arundic acid (300 μM) inhibited the activation of primary rat stellate cells, as determined by morphological transformation and α-smooth muscle actin expression, after both prophylactic and therapeutic treatment. The level of α-smooth muscle actin mRNA showed a dose-dependent decrease in response to arundic acid, and 50 μM arundic acid exhibited the maximum inhibition of collagen 1α1 mRNA expression. In contrast, arundic acid triggered an unexpected increase in mRNA and protein levels of cytoglobin, the fourth globin in mammals expressed exclusively in hepatic stellate cells. The effect of arundic acid on the level of α-smooth muscle actin mRNA was abrogated in HSCs treated with cytoglobin siRNA. Arundic acid decreased the expression of collagen 1α1 mRNA in LX-2 cells. CONCLUSION Arundic acid affects the activation process of hepatic stellate cells via the unexpected induction of cytoglobin.

Decreased Transport of p-Aminohippurate in Renal Basolateral Membranes Isolated from Rats with Acute Renal Failure

Transport of D-glucose, p-aminohippurate (organic anion), and tetraethylammonium (organic cation) was studied in the renal basolateral membrane vesicles isolated from rats with acute renal failure (ARF). ARF was induced by a single injection of uranyl nitrate. Carrier-mediated transport of p-aminohippurate, estimated under anion–anion exchange condition, was significantly decreased in basolateral membrane vesicles isolated from ARF rats. In contrast, there were no significant differences in D-glucose and tetraethylammonium uptake between normal and ARF rats. When normal basolateral membrane vesicles were incubated in vitro with uranyl nitrate, no significant inhibition in p-aminohippurate uptake was observed. These results suggest that organic anion transport is decreased in renal basolateral membranes from ARF rats, and this transport dysfunction cannot be explained by the direct interaction of uranyl nitrate with the organic anion carrier.