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Biomedical subjects

T Nakadate

Publications and source records attributed to T Nakadate.

At least 91 records · Page 5Linked to original sources
PubMed1983

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion and ornithine decarboxylase activity by quercetin: possible involvement of lipoxygenase inhibition.

Quercetin (30 mumol/mouse) markedly suppressed the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA, 20 nmol/mouse) on skin tumor formation in the CD-1 mice initiated by 7,12-dimethylbenz[a]anthracene (200 nmol/mouse). TPA (20 nmol/mouse)-induced epidermal ornithine decarboxylase (ODC) activity was also inhibited by quercetin (10-30 mumol/mouse), but it failed to inhibit the stimulation of epidermal DNA synthesis by TPA. In addition, quercetin potently inhibited lipoxygenase from 105 000 g supernatant of epidermal homogenate of mice. The 50% inhibition of lipoxygenase was observed by quercetin at 1.3 microM. These results suggest that the inhibition of lipoxygenase by quercetin is one of the major actions of the above agent to inhibit tumor promotion and TPA-induced ODC activity.

Animals↗
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

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

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

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity by lipoxygenase inhibitors: possible role of product(s) of lipoxygenase pathway.

Induction of epidermal ornithine decarboxylase (ODC) by a topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter, was inhibited by treatment of mouse skin with phenidone (3-90 mumol/mouse), nordihydroguaiaretic acid (30 mumol/mouse) or 3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW 755C, 30 mumol/mouse), which are well-known lipoxygenase inhibitors. Phenidone and BW 755C are also to be cyclooxygenase inhibitors. Inhibition of TPA-induced ODC by indomethacin (1.12 mumol/mouse), a selective cyclooxygenase inhibitor, was counteracted by prostaglandin E2 (PGE2) (140 nmol/mouse). This counteracting effect of PGE2 was reversed by the treatment of mice with nordihydroguaiaretic acid (30 mumol/mouse) or phenidone (30 mumol/mouse). ODC activity which was suppressed by nordihydroguaiaretic acid or phenidone at a dose of 180 mumol/mouse was not further inhibited by indomethacin (1.12 mumol/mouse). In addition, the counteracting action of PGE2 (140 nmol/mouse) was not observed in mice treated with nordihydroguaiaretic acid or phenidone at a dose of 180 mumol/mouse. Thus, the suppressive effect of nordihydroguaiaretic acid or phenidone on the ODC induction by TPA would be due to the inhibition of lipoxygenase. The above findings strongly suggest that not only cyclooxygenase product (i.e., PGE2) but also lipoxygenase product(s) are involved in the mechanism of ODC induction in mouse epidermis, and a lack of either cyclooxygenase product or lipoxygenase product(s) causes a failure of ODC induction by TPA.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1982

Involvement of alpha 1-adrenergic receptors in the inhibitory effect of catecholamines on the thyrotropin-induced release of thyroxine by the mouse thyroid.

TSH enhanced the release of T4 from the mouse thyroid incubated in vitro. Norepinephrine, a nonspecific alpha-adrenergic agonist, and methoxamine, an alpha 1-agonist, inhibited the TSH-stimulated release of T4 at 10(-4) and 10(-5) M, whereas clonidine, an alpha 2-agonist, exerted a weak inhibition. The inhibitory effect of 10(-5) M norepinephrine on the T4 release stimulated by TSH was prevented by prazosin, an alpha 1-antagonist, at concentrations higher than 10(-7) M, whereas yohimbine, an alpha 2-antagonist, exerted weak activity in antagonizing the inhibition induced by norepinephrine. Norepinephrine, methoxamine, and clonidine did not significantly reduce the cAMP accumulation stimulated by TSH in the mouse thyroid incubated in vitro. These findings in the mouse thyroid indicate that catecholamines act by way of alpha 1-adrenergic receptors to suppress TSH-stimulated release of T4 without reducing the cAMP levels stimulated by TSH in the mouse thyroid.

Animals↗
PubMed1982

Alpha-2 adrenergic inhibition of intestinal secretion induced by prostaglandin E1, vasoactive intestinal peptide and dibutyryl cyclic AMP in rat jejunum.

Effects of alpha adrenergic agents on intestinal secretion induced by prostaglandin E1 (PGE1), vasoactive intestinal peptide (VIP) and dibutyryl cyclic AMP (Bt2cAMP) were investigated in rat jejunum in vivo. Oxymetazoline and clonidine were more potent than epinephrine in inhibiting the PGE1-induced secretion. Methoxamine failed to inhibit the PGE1-induced secretion even with a 100-fold higher dose than that of clonidine. A high dose (1 mumol/kg) of oxymetazoline not only inhibited the PGE1- induced secretion but also enhanced net fluid absorption. Yohimbine reversed the inhibitory effect of clonidine, whereas phenoxybenzamine did not. These antagonists per se did not produce any effects on PGE1-induced secretion. Clonidine inhibited the intestinal secretion induced by VIP or Bt2cAMP, whereas methoxamine did not. The inhibitory effect of clonidine was reversed by yohimbine. Phenoxybenzamine per se inhibited intestinal secretion induced by either VIP or Bt2cAMP. Clonidine did not produce any significant effects on PGE1- augmented cAMP levels in jejunal mucosa in vivo. These results suggest that stimulation of alpha-2 adrenoceptors in rat jejunal mucosa inhibits some mechanisms distal to cAMP generation and in turn results in the inhibition of net water intestinal secretion. These findings also raise the question of general validity of a hypothesis that alpha-2 adrenoceptors regulate cellular functions through the inhibition of adenylate cyclase activity.

Adrenergic alpha-Agonists↗
PubMed1982

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity by phospholipase A2 inhibitors and lipoxygenase inhibitor.

Application of 12-O-tetradecanoylphorbol-13-acetate (TPA; 20 nmol/mouse), a tumor-promoting agent, to mouse skin results in an induction of epidermal ornithine decarboxylase (ODC; EC 4.1.1.17). Induction of ODC by TPA was inhibited by treatment of skin with indomethacin (1.12 mumol/mouse), a cyclooxygenase inhibitor, and the ODC activity suppressed by indomethacin was completely restored by concurrent application of prostaglandin E2 (PGE2) (140 nmol/mouse) as described first by Verma et al. (Cancer Res., 40: 308-315, 1980). Treatment of mice with tetracaine (20 and 100 mumol/mouse), a nonspecific phospholipase A2 inhibitor, inhibited the induction of ODC by TPA. More specific phospholipase A2 inhibitors, mepacrine (20 mumol/mouse) and p-bromophenacyl bromide (10 mumol/mouse), also inhibited the ODC induction. The TPA-induced ODC inhibited by mepacrine was not restored by the treatment of mice with PGE2. TPA-induced ODC inhibited by either mepacrine or p-bromophenacyl bromide was partially but significantly restored by treatment with arachidonic acid (1 to 40 mumol/mouse). Neither PGE2 nor arachidonic acid alone could induce the epidermal ODC. Treatment of mice with nordihydroguaiaretic acid (10 to 90 mumol/mouse), a lipoxygenase inhibitor, also inhibited the induction of ODC by TPA. These results strongly indicate that the stimulation of phospholipase A2 activity is a crucial process in inducing mouse epidermal ODC by TPA and not only cyclooxygenase product (i.e., PGE2) but also lipoxygenase product(s) are involved in the mechanism of ODC induction. Our present data also suggest that the above arachidonate metabolites are essential but not sufficient factors for the TPA-stimulated induction of ODC.

Animals↗
PubMed1982

Cross-sectional study of pulmonary function in cadmium alloy workers.

Two groups of cadmium workers (7 and 9 men) and a group of reference workers (122 men) were studied for the purpose of determining the pulmonary effects of cadmium. Indices of pulmonary function, based on the forced expiratory flow volume curve and respiratory impedance, were measured for all the groups, and indicators of cadmium exposure and effects on renal tubular reabsorption functions were also measured in the two groups of cadmium workers. The mean blood and urinary levels of cadmium were 2.08 microgram/100 ml (185.06 nmol/l) and 32.6 microgram/l (290.04 nmol/l), respectively, and the level of inhalation exposure was estimated at about 1 mg/m3 as the 8-h average concentration for about 5 a in the high exposure group. The percentage of the predicted function values of the highly exposed workers was significantly deteriorated for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), peak expiratory flow, maximum expiratory flow at 75, 50, and 25% of the FVC, percentage of FEV1.0 to FVC, and respiratory impedance, whereas those of the slightly exposed workers were reduced only for FVC and FEV1.0. A paired comparison between the highly exposed workers and matched referents disclosed the same results. It was concluded that chronic obstructive pulmonary changes had been induced by cadmium in Japanese workers without a history of acute or subacute cadmium pneumonitis.

Adult↗
PubMed1981

Adrenergic receptors and the onset of streptozotocin-induced diabetes in mice.

Treatment with yohimbine, an alpha 2-adrenergic blocker, prior to the injection of a subdiabetogenic dose of streptozotocin (STZ) produced hyperglycemia and hypoinsulinemia in mice 7 days later. Prazosin, an alpha 1-adrenergic blocker, was ineffective. The capacity of phentolamine and phenoxybenzamine to potentiate the diabetogenic effect of STZ was intermediate between that of yohimbine and prazosin. Propranolol and hexamethonium inhibited the potentiating action of yohimbine. Yohimbine enhanced the potentiating effect of isoproterenol on the STZ-induced diabetes. Acute changes in phase glucose and insulin levels induced by STZ were potentiated by yohimbine but not by prazosin. The insulin releasing ability of the pancreatic islets 7 days after STZ was all but lost in mice pretreated with yohimbine but not with prazosin. These results suggest that the beta- and alpha 2-, not alpha 1-adrenergic system which modulates insulin release from pancreatic islets influences the response to the diabetogenic action of STZ in mice.

Adrenergic alpha-Antagonists↗