Search PubMed⌕ Search

Biomedical subjects

R Kato

Publications and source records attributed to R Kato.

At least 613 records · Page 34Linked to original sources
PubMed1983

Antitumor effect and metabolic activation of cyclophosphamide and 4-hydroperoxycyclophosphamide in the human breast carcinoma (MX-1)-nude mouse system.

The effects of cyclophosphamide (CPA) and its active form, 4-hydroperoxy-CPA, against human breast carcinoma transplanted into nude mice (BALB/c nu/nu) were evaluated in terms of the decreases of hepatic drug-metabolizing enzymes in nude mice. A human breast carcinoma, MX-1, was implanted into the subcutaneous tissue of nude mice and a drug was administered intravenously once at a dose of 0.05, 0.1 or 0.15 mmol/kg, 1 or 3 weeks after tumor inoculation. 4-Hydroperoxy-CPA was more effective than CPA as regards inhibition of tumor growth, and the difference in effect was greater when the drugs were administered 3 weeks after tumor inoculation. The activity of CPA was depressed by the decrease of the hepatic drug-metabolizing enzymes in proportion to the tumor-bearing period. Therefore, the effects of masked derivatives of CPA may correlate with the changes in drug-metabolizing activities of tumor-bearing mice. The human tumor xenografts-nude mice system is considered to be suitable for chemosensitivity tests with masked compounds.

Adult↗
PubMed1982

Insulinotropic effects of exogenous phospholipase A2 and C in isolated pancreatic islets.

In isolated pancreatic islets of rats, exogenous phospholipase A2 produced concentration-dependent insulin secretion. p-Bromophenacyl bromide-treated enzyme no longer showed the insulinotropic effect. The insulinotropic effect of phospholipase A2 was inhibited by nordihydroguaiaretic acid (NDGA) and 1-phenyl-3-pyrazolidinone (Phenidone) but not by indomethacin. Exogenous phospholipase C also demonstrated a concentration-related insulinotropic effect. The phospholipase C-induced insulin secretion, however, was inhibited by none of the above inhibitors. These results indicate that a lipoxygenase product(s) is involved in the insulinotropic action of phospholipase A2.

Animals↗
PubMed1982

Evidence for the involvement of multiple forms of cytochrome P-450 in the occurrence of sex-related differences of drug metabolism in the rat.

Multiple forms of cytochrome P-450 in liver microsomes of untreated male and female rats could be divided into several fractions by the use of omega-amino-n-octyl Seph. 4B and DE-52 columns. Male cytochrome P-450 fractions (I-b - I-e) differed from female fractions (I-b - I-e) with respect to absorption peaks in carbon monoxide difference spectra and 7-propoxycoumarin O-depropylation activities. Although male and female I-a fractions showed quite similar protein bands on SDS-polyacrylamide gel electrophoresis, some protein bands in other male fractions (I-b - I-e) were absent in corresponding female fractions. Immunochemical examinations using immunoglobulin G raised to cytochrome P-450 purified from untreated male rats also showed that liver microsomes from male and female rats contain different forms of cytochrome P-450. Based on these results, we propose that sex-related differences of drug metabolizing activities in liver microsomes are caused by multiple forms of cytochrome P-450.

Animals↗
PubMed1982

Involvement of alpha 1-adrenergic receptors in stimulation of phosphatidylinositol metabolism by catecholamines in mouse thyroids.

The effects of alpha-adrenergic agonists and thyroid stimulating hormone on the incorporation of radioactive phosphate into phosphatidylinositol were investigated in mouse thyroids in vitro. The incorporation of 32P orthophosphate into phosphatidylinositol was stimulated by thyroid stimulating hormone, norepinephrine (a mixed alpha 1- and alpha 2-adrenergic agonist), methoxamine and phenylephrine (alpha 1-agonists) and slightly by clonidine and oxymetazoline (alpha 2-agonists) but not by isoproterenol (beta-agonist). Prazosin (alpha 1-antagonist) inhibited the stimulation by norepinephrine of 32P incorporation into phosphatidylinositol, but yohimbine (alpha 2-antagonist) was less effective. Although norepinephrine inhibits the thyroid stimulating hormone-induced release by activating alpha-, especially alpha 1-adrenoceptors in mouse thyroids [M. L. Maayan et al., Metabolism 26, 473 (1977); M. L. Maayan et al., Endocrinology 101, 284 (1977); T. Muraki et al., Endocrinology 110, 51 (1982)] alpha 1-agonists did not decrease the stimulation of turnover elicited by thyroid stimulating hormone and did not have additive action with it. These results suggest that (1) the stimulation of phosphatidylinositol turnover of mouse thyroids elicited by adrenergic agonists is mediated by activation of alpha 1-adrenoceptors and (2) the inhibitory effect of norepinephrine on the thyroid stimulating hormone-induced release of thyroxine is not mediated by norepinephrine-inhibition of phosphatidylinositol-turnover stimulated by thyroid stimulating hormone.

Adrenergic alpha-Agonists↗
PubMed1982

Prevention of glucose-induced insulin secretion by lipoxygenase inhibitor.

Glucose-induced insulin secretion was investigated using isolated pancreatic islets of rats. The phospholipase A2 inhibitors. p-bromophenacyl bromide (0.1 mM) and mepacrine (0.1 mM) inhibited glucose-induced insulin secretion. Indomethacin (5 microM), a cyclooxygenase inhibitor, failed to inhibit glucose-induced insulin secretion, while the lipoxygenase inhibitor nordihydroguaiaretic acid (0.1-0.2 mM) inhibited it. These results suggest that stimulation of phospholipase A2 and a product(s) formed by the lipoxygenase pathway play an important role in the glucose-induced insulin secretion.

Animals↗
PubMed1982

Development of clonidine-tolerance in the rat vas deferens: cross tolerance to other presynaptic inhibitory agents.

Possibility of the development of clonidine-tolerance in the peripheral nervous tissue was examined using vas deferens isolated from rats chronically treated with clonidine. Rats were treated with clonidine for 10 days by adding the drug to drinking water (10 microgram/ml). For the control rats, drug-free tap water was provided. Electrically evoked twitch response of vas deferens was suppressed by adenosine, beta-endorphine and alpha 2-adrenergic agonists, such as clonidine and B-HT 933, both in control and clonidine-treated groups. Vas deferens isolated from clonidine-treated rats showed significantly lower responsiveness to the inhibitory effects of clonidine and B-HT 933 compared to those from control rats. Vas deferens from clonidine-treated rats also was less responsive to adenosine and beta-endorphin, both of which interact with presynaptic inhibitory receptors other than alpha 2-adrenoceptors. On the other hand, responsiveness of the postsynaptic smooth muscle to both alpha-adrenergic and muscarinic cholinergic stimulation did not change after 10 days of treatment with clonidine. These results suggest that clonidinetolerance can be induced in the peripheral nervous system by chronic treatment of this drug and that the tolerance is not specific to alpha 2-adrenergic agonists. Some common pathway in the inhibitory mechanisms of various agents or possible interactions between the different types of presynaptic inhibitory receptors may be involved in this phenomenon.

Adenosine↗
PubMed1982

Strain difference in morphine-induced increase in plasma cyclic AMP and cyclic GMP levels in relation to locomotor activity in male mice.

The effects of morphine on plasma cyclic nucleotide levels and on locomotor activity were investigated in four inbred strains of male mice. Morphine increased both cyclic AMP and cyclic GMP levels as well as locomotor activity in C57BL/6N mice. In BALB/cAnN mice, morphine increased plasma cyclic GMP levels and motor activity without changes in plasma cyclic AMP levels. In C3H/HeN mice, morphine increased plasma cyclic GMP levels without changing cyclic AMP levels and motor activity, but neither plasma cyclic nucleotide levels nor motor activity were increased by morphine in DBA/2N mice. Epinephrine and carbachol increased plasma cyclic AMP and cyclic GMP levels, respectively, in both C57BL and DBA mice. These results show that there is a significant strain difference in the effects of morphine on plasma cyclic nucleotide levels as well as motor activity. The major cause of strain difference in the effects of morphine on cyclic nucleotide levels is unlikely to be due to the difference in the regulation of adenylate cyclase linked to adrenoceptors or that of guanylate cyclase connected with cholinoceptors.

Animals↗
PubMed1982

Alpha 2-adrenoceptors inhibit the cholera-toxin-induced intestinal fluid accumulation.

The effects of adrenoceptor agonists and antagonists on the cholera-toxin-induced intestinal fluid accumulation and the mucosal levels of cAMP were investigated in vivo. Cholera toxin produced a marked fluid accumulation. Adrenaline inhibited the effect of the toxin in a dose-dependent manner. An alpha 2-adrenoceptor blocking agent yohimbine antagonized the effect of adrenaline. The alpha 1-adrenoceptor blocking agents prazosin and phenoxybenzamine failed to antagonize the effect of adrenaline. A high dose of a beta-adrenoceptor blocking agent pindolol did not antagonize the effect of adrenaline. Yohimbine or pindolol alone did not produce any effects on the toxin-induced fluid accumulation. However, prazosin and phenoxybenzamine per se inhibited the toxin-induced fluid accumulation. An alpha 2-selective agonist clonidine was slightly more potent than adrenaline, and was about 100-fold more potent than the alpha 1-selective agonist methoxamine in inhibiting the cholera-toxin-induced intestinal secretion. Clonidine, adrenaline and methoxamine failed to reduce the mucosal levels of cAMP, while these alpha-adrenoceptor agonists inhibited the toxin-induced fluid accumulation in the same preparations. These results suggest that the stimulation of alpha 2-adrenoceptors inhibit the cholera-toxin-induced intestinal secretion without reducing the whole mucosal levels of cAMP.

Adrenergic alpha-Agonists↗
PubMed1982

Inhibitory alpha 2-adrenergic mechanism regulating gastric secretion in pylorus-ligated rats.

Several alpha-adrenoceptor agonists given intracerebroventricularly or subcutaneously to rats were assessed for their effects on gastric secretion under condition of pylorus ligation. Intracerebroventricular injection of alpha-adrenoceptor agonists reduced gastric secretion, in the following order (relative potency, clonidine = 1): oxymetazoline (100) greater than clonidine (1) greater than methoxamine (0.024) greater than phenylephrine (0.003). The antisecretory effects of oxymetazoline and clonidine given intracerebroventricularly were antagonized with yohimbine administered by the same route. Subcutaneous injection of alpha-adrenoceptor agonists also reduced gastric secretion, in the following order (relative potency, clonidine = 1): clonidine (1) greater than oxymetazoline (0.3), much greater than phenylephrine (0.001) approximately methoxamine (0.0006). Oxymetazoline, when given intracerebroventricularly, was most effective in decreasing the volume and titratable acidity of gastric secretion. Pretreatment with 6-hydroxydopamine intracerebroventricularly (250 micrograms/rat x 2; 72 and 120 h before) reduced the antisecretory effect of clonidine given intracerebroventricularly. Thus, gastric secretion appears to be regulated in an inhibitory manner by alpha 2-, but not by alpha 1- adrenoceptors in the central and peripheral nervous systems, in pylorus-ligated rats.

Adrenergic alpha-Agonists↗
PubMed1982

Metabolic activation of 2-amino-9H-pyrido[2,3-b]indole by rat-liver microsomes.

Microsomal activation was required for the expression of the mutagenicity of 2-amino-9H-pyrido[2,3-b]indole (A alpha C) toward Salmonella typhimurium TA98. Pretreatment of rats with PCB, 3-methylcholanthrene or phenobarbital increased the mutagenic activating ability of hepatic microsomes by 16-, 10- and 2-fold, respectively, as compared with the untreated. The mutagenic activation of A alpha C by microsomes from PCB-treated rats was inhibited by ellipticine and alpha-naphthoflavone, whereas SKF 525-A and metyrapone showed a slight or no inhibitory effect, indicating that the P-448 form of cytochrome P-450 is involved in the mutagenic activation of A alpha C. Metabolic activation of A alpha C was studied by a high-performance liquid chromatography and Salmonella/microsome assay system, and the mutagenic metabolites formed were determined to be the N-hydroxy and nitroso derivatives, from the results of reaction with oxidizing or reducing agents. These results strongly indicate that N-hydroxylation of A alpha C by the P-448 type of cytochrome P-450 is essential for the mutagenic activation.

Animals↗