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R Hori

Publications and source records attributed to R Hori.

At least 163 records · Page 9Linked to original sources
PubMed1986

H+ gradient-dependent transport of aminocephalosporins in rat intestinal brush-border membrane vesicles. Role of dipeptide transport system.

The transport of cephalosporin antibiotics in brush-border membrane vesicles isolated from rat small intestine has been studied by a rapid filtration technique, demonstrating a carrier-mediated transport system for aminocephalosporins such as cephradine. In agreement with the transport mechanisms of dipeptides, the uptake of cephradine by brush-border membrane vesicles was Na+-independent and was stimulated in the presence of an inward H+ gradient ([H+]o greater than [H+]i). Cephradine uptake in the presence of an inward H+ gradient was a saturable process with an apparent Km of 9.4 mM, and was markedly inhibited by dipeptides but not inhibited by amino acids. The present data suggest that aminocephalosporins can be transported by a common carrier-mediated system with dipeptides in the intestinal brush-border membranes and this process may be driven by an H+ gradient.

Amines↗
PubMed1986

Role of chloride on carrier-mediated transport of p-aminohippurate in rat renal basolateral membrane vesicles.

Effect of inorganic anions on p-amino[3H]hippurate transport in renal basolateral membranes has been studied using the vesicles preloaded with unlabeled p-aminohippurate (countertransport condition). The uptake of p-amino[3H]hippurate was stimulated by the outward gradient of unlabeled p-aminohippurate and the labeled substrate was accumulated into the vesicles against its concentration gradient in the presence of Cl-. The substitution of SCN- and SO4(2-) for Cl- in both sides of the vesicles depressed the initial rate and the overshoot magnitude of p-amino[3H]hippurate uptake. These results suggest that Cl- may play an important role for the carrier-mediated transport system of organic anion in renal basolateral membranes.

Aminohippuric Acids↗
PubMed1986

Pharmacokinetics and antiarrhythmic activity of ajmaline in rats subjected to coronary artery occlusion.

The pharmacokinetics and the antiarrhythmic action of intravenous ajmaline were investigated in anaesthetized rats subjected to coronary artery occlusion. Ajmaline (0.125-2 mg kg-1, i.v. given just after occlusion) suppressed arrhythmias in a dose-dependent manner, judged by the reduction of premature ventricular complexes. The incidence of malignant arrhythmias (ventricular tachycardia and fibrillation) was preferentially suppressed at the higher doses of ajmaline (1 and 2 mg kg-1). Coronary occlusion induced a change in pharmacokinetics of ajmaline (2 mg kg-1) and its total body blood clearance was significantly decreased from 56.6 ml min-1 kg-1 in sham-operated rats to 43.1 ml min-1 kg-1 in rats after coronary occlusion. Ajmaline exhibited a significantly increased negative dromotropic action (increased PQ interval) in rats after coronary occlusion compared with that in sham-operated rats. The difference seems to be due to the pharmacokinetic change since the concentration-effect relationship was similar in the two groups of rats. We suggest that the measurement of drug levels is important in the assessment of antiarrhythmic agents.

Ajmaline↗
PubMed1986

Mechanisms of pharmacokinetic interaction between ajmaline and quinidine in rats.

In order to elucidate the mechanism of ajmaline-quinidine interaction previously observed in humans, the effects of quinidine on pharmacokinetics of ajmaline were investigated in rats. Concurrent oral administration of 10 mg/kg of quinidine markedly increased the plasma concentration of ajmaline at a dose of 2 mg/kg. On the other hand, it did not affect the pharmacokinetics of ajmaline after intravenous dose. The availability of ajmaline after oral dose showed an increase from 13% to nearly 100% by the presence of quinidine, which suggests a change in the presystemic clearance of ajmaline. In fact, when ajmaline was administered into the intestinal loop, its concentration in mesenteric venous plasma increased approximately 5-fold by the combination with quinidine. Furthermore, quinidine delayed the elimination rate of ajmaline from the perfused rat liver. These results indicate that quinidine prevents presystemic elimination of ajmaline in the intestine and liver, and increases the systemic availability of ajmaline.

Ajmaline↗
PubMed1986

Mechanisms of gentamicin transport in kidney epithelial cell line (LLC-PK1).

The characteristics of gentamicin transport have been studied by using cultured kidney epithelial cell line LLC-PK1. The uptake of gentamicin by the LLC-PK1 cells appeared to be linear for 30 min and reached the equilibrium at day 1. Marked stimulation of gentamicin uptake was observed on the development of a confluent cell density, accompanied by the increases of marker enzyme activities and Na+-dependent D-glucose transport in the apical membranes. Gentamicin uptake was inhibited by metabolic inhibitors such as rotenone and 2,4-dinitrophenol, and was inhibited competitively in the presence of other aminoglycosides. Depending on the external calcium concentration, calcium ionophore A23187 stimulated gentamicin uptake, whereas ethylene glycol bis(beta-aminoethyl ether)N,N1-tetraacetic acid, a calcium chelator, inhibited gentamicin uptake. These results suggest that gentamicin uptake by the LLC-PK1 cells may be mediated via specialized transport system, and calcium ion movement may play an important role as a regulatory factor for this transport system.

Aminoglycosides↗
PubMed1986

An analysis program MULTI(ELS) based on extended nonlinear least squares method for microcomputers.

An analysis program MULTI(ELS) was developed for population pharmacokinetics on a microcomputer. The program based on the extended least squares (ELS) is written in the Microsoft minimum BASIC command alone. ELS simultaneously estimates not only the population pharmacokinetic parameters but also the variances of inter-individual variabilities around the population parameters and of intra-individual variabilities for the plural time courses, whereas the ordinary least squares estimates the pharmacokinetic parameters of each time course. Two least squares algorithms (i.e. quasi-Newton and simplex methods) are provided in MULTI(ELS). MULTI(ELS) was compared with NONMEM (Version I, Level 3) developed by Sheiner and Beal for several time course data. It was shown that MULTI(ELS) gave the same results as NONMEM. MULTI(ELS) calculates the Akaike's information criterion (AIC) for the extended least squares. It was also shown that the AIC is effective in comparing the population characteristics of time courses in a group with those in another group and in verifying the model structures of population means, inter-individual variations and intra-individual variations.

Computers↗
PubMed1985

Distinction of three types of D-glucose transport systems in animal cells.

Immunoblotting of plasma membrane fractions from rat kidney cortex with antibody to human erythrocyte glucose transporter showed a single major cross-reacting material of 48K in basolateral membrane fractions possessing a facilitated diffusion system for D-glucose, but not in brush border membrane fractions which have a Na-dependent active transport system. Cytochalasin B inhibited D-glucose uptake in basolateral membrane vesicles but not in brush border vesicles. Cross-reacting materials of 44-55K were detected in several animal cells exhibiting facilitated diffusion systems, including a hormone dependent system. These results indicate molecular difference between glucose transporters of facilitated diffusion systems and active transport systems.

Adipose Tissue↗
PubMed1985

Cimetidine transport in rat renal brush border and basolateral membrane vesicles.

The transport of cimetidine by rat renal brush border and basolateral membrane vesicles has been studied in relation to the transport system of organic cation. Cimetidine inhibited [3H]tetraethylammonium uptake by basolateral membrane vesicles in a dose dependent manner, and the degree of the inhibition was almost the same as that by unlabeled tetraethylammonium. In contrast, cimetidine inhibited the active transport of [3H]tetraethylammonium by brush border membrane vesicles more strongly than unlabeled tetraethylammonium did. In agreement with the transport mechanism of tetraethylammonium in brush border membranes, the presence of an H+ gradient ([H+]i greater than [H+]o) induced a marked stimulation of cimetidine uptake against its concentration gradient (overshoot phenomenon), and this concentrative uptake was inhibited by unlabeled tetraethylammonium. These results suggest that cimetidine can share common carrier transport systems with tetraethylammonium in renal brush border and basolateral membranes, and that cimetidine transport across brush border membranes is driven by an H+ gradient via an H+-organic cation antiport system.

Animals↗
PubMed1985

Specific binding activities and cyclic GMP responses by atrial natriuretic polypeptide in kidney epithelial cell line (LLC-PK1).

Receptor binding activities and cyclic GMP responses by alpha-human atrial natriuretic polypeptide (alpha-hANP) and its fragments were studied in a kidney epithelial cell line (LLC-PK1). Binding of 125I-alpha-hANP to the cells at 0 degrees C was saturable, time-dependent and reversible, indicating the presence of a single class of binding sites. alpha-hANP (7-23)NH2 fragment inhibited most effectively the specific binding of 125I-alpha-hANP to the LLC-PK1 cells, followed by alpha-hANP (17-28) and alpha-hANP (8-22), while alpha-hANP (1-6) and alpha-hANP (24-28) did not. alpha-hANP stimulated the formation of cyclic GMP in the LLC-PK1 cells dose-dependently. Although no fragments of alpha-hANP used were effective for cyclic GMP formation in the LLC-PK1 cells, alpha-hANP (7-23) NH2 antagonized the action of alpha-hANP on cyclic GMP formation. These data suggest that the LLC-PK1 cells retain specific receptors for atrial natriuretic polypeptide (ANP) and respond to ANP by stimulating cyclic GMP formation, and therefore this cell line may be useful for studying the mechanism of action for ANP in renal tubular cells.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Identification of the major binding protein of salmon calcitonin in the rat.

The major serum binding protein of salmon calcitonin (sCT) in the rat was identified. High-molecular-weight (HMW) forms of sCT, produced by the incubation of radioactive sCT in rat serum, were isolated by gel filtration and analysed by chromatofocusing. The major radioactive peak was eluted at the region of albumin in gel filtration, and this peak had a slightly higher pI than albumin on chromatofocusing. Immunoreactivity of the radioactive peak fraction in chromatofocusing, examined by immunodiffusion, showed that the major protein in the fraction was albumin. Immunoreactivity of the radioactive HMW fraction isolated by gel filtration was studied by immunoprecipitation, indicating that a large portion of the fraction reacted with anti-rat albumin antiserum. These results suggested that the radioactive peak in chromatofocusing represents the complex of sCT and rat albumin. Further, HMW forms of sCT were analysed by immunoelectrophoresis and autoradiography, and most of the radioactivity was found on the precipitation line of albumin. These results demonstrate that the major binding protein of sCT in rat serum is albumin.

Animals↗
PubMed1985

Reduced hepatic uptake of propranolol in rats with acute renal failure.

The effect of acute renal failure (ARF) on the hepatic uptake and metabolism of propranolol was investigated in relation to the hepatic clearance of the drug. ARF was induced by the subcutaneous injection of uranyl nitrate to rats. The uptake rate of propranolol in the isolated perfused liver was determined by the multiple-indicator dilution method and was found to decrease from 43.6 +/- 2.0 min-1 (mean +/- S.E.) in control to 29.4 +/- 1.7 min-1 in ARF (P less than 0.001). The recovery fraction of propranolol in effluent venous blood increased about twofold in ARF compared to control (P less than 0.05). The metabolic activity for propranolol was examined using the hepatic microsomal fraction prepared from control and ARF rats. There was no significant difference in the kinetics of oxidative metabolism of propranolol between two groups. These results suggest that the previously reported decrease in the hepatic clearance of propranolol in ARF is due to decreased hepatic uptake of the drug from the blood into the liver cells.

Acute Kidney Injury↗
PubMed1985

Specific receptors for atrial natriuretic polypeptide on basolateral membranes isolated from rat renal cortex.

The binding of alpha-human atrial natriuretic polypeptide (alpha-hANP) to brush border and basolateral membranes isolated from the rat renal cortex was studied at 0 degree C by a rapid filtration technique. Specific binding of 125I-alpha-hANP to basolateral membranes reached a steady state at 4 hr. The binding to brush border membranes was maximal at 5-15 min and then rapidly decreased. The analysis of incubation mixtures with basolateral membranes revealed little degradation of 125I-alpha-hANP during the 4-hr incubation, while there was extensive degradation of the ligand with brush border membranes during the 30-min incubation. High affinity binding of 125I-alpha-hANP was demonstrated on basolateral membranes but not on brush border membranes. These data suggest that specific receptors for alpha-hANP are localized on basolateral membranes of the renal cortex.

Animals↗
PubMed1985

H+-gradient-dependent active transport of tetraethylammonium cation in apical-membrane vesicles isolated from kidney epithelial cell line LLC-PK1.

Transport of [3H]tetraethylammonium (NEt4+), an organic cation, has been studied by using apical-membrane vesicles isolated from cultured kidney epithelial cell line LLC-PK1. The uptake of NEt4+ by apical-membrane vesicles was osmotically sensitive, time-dependent and saturable. The presence of an H+ gradient ([H+]i greater than [H+]o) induced a marked stimulation of NEt4+ uptake against its concentration gradient (overshoot phenomenon), and this concentrative uptake was inhibited by HgCl2. These results suggest that apical membranes isolated from the LLC-PK1 cells retain the transport characteristics of NEt4+ similar to those observed in renal brush-border membranes.

Animals↗
PubMed1985

High molecular weight derivative of salmon calcitonin with prolonged hypocalcemic activity.

A new method preparing a long-acting formula of salmon calcitonin, which possesses high specific activity, has been developed. This method consists of two processes: (a) preparation of a high molecular weight derivative of salmon calcitonin and (b) preparation of a zinc suspension of the derivative. The derivative was prepared by the incubation of reduced salmon calcitonin with bovine serum albumin. Although it retained almost the same biological activity as the original calcitonin, it was not longer acting. Addition of zinc to the solution of the derivative resulted in a suspension with biological activity significantly longer than the original calcitonin. This procedure is described for obtaining a sustained-release preparation of salmon calcitonin, which might be useful for other peptide drugs.

Animals↗
PubMed1985

A new dosing regimen in renal insufficiency: application to cephalexin.

We describe a new method of drug dosage adjustment. The method simultaneously considers glomerular and tubular functions as parameters, because nonparallel decreases in both functions limit the use of the conventional endogenous creatinine clearance (CLCR) method for dosage adjustment. In the new method, CLCR and the 15-minute phenolsulfonphthalein (PSP15') test were used and applied to patients with renal insufficiency with cephalexin (CEX) as a model drug for renal tubular secretion. The results clearly demonstrate good control of plasma CEX concentrations by the CLCR-PSP15' method, whereas there were marked changes in plasma CEX levels with the CLCR method alone. Our method appears to be more useful for patients with renal impairment than the conventional CLCR method for CEX, which is mainly excreted in urine by renal tubular secretion. A nomogram for the CEX dosing interval is proposed for application to clinical practice.

Absorption↗
PubMed1985

A nonlinear multiple regression program, MULTI2 (BAYES), based on Bayesian algorithm for microcomputers.

A nonlinear multiple regression analysis program MULTI2(BAYES) was developed for microcomputers. The Bayesian algorithm which is incorporated in MULTI2 (BAYES) combines the insufficient individual patient data (individual data) with the pharmacokinetic parameters published in literatures (population parameters) to predict the plasma time course of the patient. The program is written in the minimum Microsoft BASIC commands alone to be executable on many personal computers without any modification. The numbers of parameters to estimate, independent variables and dependent variables are not restricted in use of MULTI2(BAYES). The pharmacokinetic models are defined as one pleases by the user. The four nonlinear least squares algorithms, i.e. Gauss-Newton method, damping Gauss-Newton method, modified Marquardt method by Fletcher and simplex method can be selected at user's option. MULTI2(BAYES) calculates the confidence limits of time courses at 95% significant level.

Computers↗
PubMed1985

Fate of porcine and human insulin at the subcutaneous injection site. I. Degradation and absorption of insulins in the rat.

The plasma insulin and serum glucose levels were compared after the subcutaneous and intravenous administration of porcine and human insulin in rats. While no difference was observed in plasma insulin or serum glucose levels with either insulin after intravenous administration, the plasma insulin levels and hypoglycemic effects of human insulin were greater than those of porcine insulin after subcutaneous administration. At various time intervals, radioactivity in subcutaneous tissue was assayed for insulin and/or its metabolites by gel filtration. Using these data, the absorption and degradation rate constants of these substances were estimated according to a one-compartment model. The degradation rate constants of human insulin was approximately half of that for porcine insulin.

Anesthesia↗