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Biomedical subjects

R Kato

Publications and source records attributed to R Kato.

At least 559 records · Page 31Linked to original sources
PubMed1984

Inhibition of calcium uptake and catecholamine release by 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) in cultured bovine adrenal chromaffin cells.

Effects of intracellular calcium antagonists, 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) and 1-(5-(p-nitrophenyl)-furfurylidene-amino) hydantoin sodium hydrate (dantrolene sodium), on catecholamine release and 45Ca2+ uptake were studied using cultured bovine adrenal chromaffin cells. TMB-8 inhibited carbamylcholine-evoked catecholamine release and 45Ca2+ uptake in a concentration-dependent manner with a similar potency. On the contrary, dantrolene sodium did not show obvious inhibitory effects of catecholamine release and 45Ca2+ uptake. Although TMB-8 inhibited the high K+-evoked catecholamine release and 45Ca2+ uptake, the potency of the drug was approximately 100-fold less than when used to inhibit the carbamylcholine-evoked catecholamine release and 45Ca2+ uptake. The inhibitory effect of TMB-8 on the carbamylcholine-evoked catecholamine release was not overcome by an increase in an extracellular calcium concentration, and was not due to competitive antagonism at the nicotinic receptor site. Moreover, TMB-8 inhibited the carbamylcholine-stimulated 45Ca2+ efflux, but dantrolene sodium failed to affect it. These results suggest that TMB-8, a well-known intracellular calcium antagonist, prevents the cellular calcium uptake in cultured adrenal chromaffin cells, and thus prevents catecholamine release.

Adrenal Glands↗
PubMed1984

Glutathione conjugation of arylnitroso compound: detection and monitoring labile intermediates in situ inside a fast atom bombardment mass spectrometer.

The glutathione (GSH) conjugation reaction of the active metabolite of a potent protein-pyrolysate carcinogen, 2-nitroso-6-methyldipyrido[1,2-a:3',2'-d]imidazole (NO-Glu-P-1), occurred in glycerol matrix inside a fast atom bombardment (FAB) mass spectrometer. The short lived GSH-conjugates were detected by in situ FAB analysis. The precursor-product relationship between the conjugates was indicated by following the reaction by measuring [M + H]+ ions of the conjugates.

Biotransformation↗
PubMed1984

Effects of inhibitors of arachidonic acid metabolism on calcium uptake and catecholamine release in cultured adrenal chromaffin cells.

The possibility that arachidonic acid metabolism is involved in the secretory process in cultured adrenal chromaffin cells was investigated by studying the effects of lipoxygenase inhibitors and cyclooxygenase inhibitors on 45Ca2+ uptake and catecholamine release. Lipoxygenase inhibitors, which have different chemical structures, such as nordihydroguaiaretic acid (NDGA), 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline (BW755C) and 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861) all prevented the catecholamine release evoked by carbamylcholine and high K+. In contrast, cyclooxygenase inhibitors, such as aspirin and indomethacin failed to inhibit the carbamylcholine-evoked catecholamine release. Lipoxygenase inhibitors also inhibited 45Ca2+ uptake into the cells stimulated by carbamylcholine and high K+. Lipoxygenase inhibitors inhibited 45Ca2+ uptake and catecholamine release with similar potency. Slightly higher concentrations of lipoxygenase inhibitors were required to inhibit high K+-evoked effects compared to those evoked by carbamylcholine. The inhibitory effects of these inhibitors on carbamylcholine-evoked catecholamine release was different in its nature from the inhibitory effect of verapamil, a blocker of the Ca2+ channel, and was not due to a competitive antagonism at cholinergic receptor site. Moreover, these lipoxygenase inhibitors did not inhibit the binding of [3H]nitrendipine to chromaffin cell homogenate. The data suggest that lipoxygenase inhibitors prevent the catecholamine release from cultured adrenal chromaffin cells by blocking Ca2+ uptake. It might be possible that lipoxygenase product(s) is involved in the Ca2+ translocation system in these cells.

Adrenal Glands↗
PubMed1984

Inhibition of benzodiazepine and GABA receptor binding by amino-gamma-carbolines and other amino acid pyrolysate mutagens.

The effect of several pyrolysate mutagens on the benzodiazepine and GABA receptors was investigated. Of amino-gamma-carbolines, Trp-P-1 antagonized the suppressive effect of diazepam on the pentylenetetrazol-induced convulsions and death, whereas Trp-P-2 by itself precipitated seizures and death in male mice. Both Trp-P-1 and Trp-P-2 inhibited the specific binding of [3H]diazepam and [3H]muscimol in rat brain membranes mainly by increasing Kd, indicating that these gamma-carbolines bind on benzodiazepine and GABA receptors. IC50S of Trp-P-1 and Trp-P-2 on specific [3H]flunitrazepam binding were not changed by addition of GABA. The Hill coefficient of Trp-P-1 for displacing [3H]diazepam binding was about unity whereas that of Trp-P-2 was less than unity. These results suggest that Trp-P-1 and Trp-P-2 act as active antagonists or inverse agonists at benzodiazepine receptors. The convulsant effect of the gamma-carbolines may be mediated by an action on the central benzodiazepine receptors; however, the role of the effect on GABA receptors is not clear.

Animals↗
PubMed1984

Phosphorylation and dephosphorylation of human promyelocytic leukemia cell (HL-60) proteins by tumor promoter.

Human promyelocytic leukemia cell line (HL-60) has been shown to be induced to the terminal differentiation into macrophage-like cells by a tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The present studies describe the effects of TPA on the phosphorylation of HL-60 cell proteins. A rapid decrease in the phosphorylation of a 75 kD protein was observed within a few minutes after treatment with TPA. On the other hand, TPA treatment of HL-60 cells caused rapid increase in the phosphorylation of a 67 kD protein and other minor proteins. Phorbol and 4 alpha-phorbol-12,13-dodecanoate, both of which are biologically inactive derivatives of TPA, failed to cause any changes in protein phosphorylation in HL-60 cells. These results suggest that changes in protein phosphorylation are involved in mechanisms of the differentiation in HL-60 cells induced by TPA. Cell fractionation experiments revealed that 67K protein was located in cytosol. Though 75K protein also seemed to be located in cytosol, the phosphate moiety of 75K protein was almost lost during cell fractionation, suggesting that the phosphorylation of 75K protein was specifically regulated in HL-60 cells. Dimethyl sulfoxide (DMSO), retinoic acid (RA) and 1,25-dihydroxy-vitamin D3, all of which induce the differentiation in HL-60 cells, did not cause any changes in protein phosphorylation. These results suggest that the changes in protein phosphorylation are specific for TPA. The possible mechanisms of changes in protein phosphorylation by TPA were discussed.

Autoradiography↗
PubMed1984

A genetic analysis of morphine responses in mice.

To investigate whether genetic factors may play a role in the difference of the responses to morphine between inbred strains of mice, we determined the effect of morphine on the plasma cyclic nucleotides, the motor activity and the rectal temperature in the 2 progenitor strains of mice, DBA and C57BL, their F1 and F2 hybrids, and the 2 backcross progenies between F1 and parental strains. C57BL was partially dominant over DBA concerning the motor activity induced by morphine, whereas DBA was partially dominant over C57BL in terms of the increase in plasma cyclic nucleotides and the hypothermia elicited by morphine. The biometric analysis suggested that the strain difference in the effects of morphine was genetically determined except for plasma cyclic AMP, and that among these quantitative traits, the effects of morphine on motor activity and rectal temperature were controlled by more than one allelic gene pairs.

Animals↗
PubMed1984

DNA single-strand breaks by nitropyrenes and related compounds in Chinese hamster V79 cells.

The DNA single-strand breaks (SSB) induced by nitropyrenes and related compounds were studied in Chinese hamster V79 cells. 1-Nitropyrene (1-NP), 1,6-dinitropyrene (1,6-DNP), 1,8-dinitropyrene (1,8-DNP), 1-nitrosopyrene (1-NOP) and 1-aminopyrene (1-AP) caused DNA-SSB in the cells. 1-NP induced SSB most effectively among the compounds tested, though the mutagenic activity of 1-NP towards mammalian cells has been reported to be negative or marginal. 1-NOP induced SSB less effectively than 1-NP, though 1-NOP is assumed to be the intermediate to the ultimate metabolite. From in vitro experiments, this result could be explained, at least partly, by the detoxicating function of reduced glutathione (GSH) or other sulfhydryl materials.

Animals↗
PubMed1984

Potent antitumor promoting activity of N-6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin antagonist, in mouse skin tumor formation induced by 7,12-dimethylbenz[a]anthracene plus teleocidin.

A calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) markedly inhibited the promoting activity of teleocidin on formation of skin tumors in mice initiated by 7,12-dimethylbenz[a]anthracene. This result strongly indicates that the critical action of the Ca2+-calmodulin system is responsible for tumor promotion in mouse skin.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Species differences in the N-acetylation by liver cytosol of mutagenic heterocyclic aromatic amines in protein pyrolysates.

The N-acetylation of 3-amino-1-methyl-5H-pyrido[4,3-b]-indole (Trp-P-2) and other heterocyclic aromatic amine promutagens isolated originally from protein pyrolysates was investigated using liver cytosols from various animal species and acetyl-CoA as an acetyl donor. Marked species differences in the enzymatic N-acetylation activity of these heterocyclic amines were observed. The N-acetylation activity also varied among the substrates used. The N-acetylation of these heterocyclic amines by hepatic cytosols from all animal species used was much less than that of the non-heterocyclic aromatic amine carcinogen, 2-aminofluorene (2-AF): the N-acetylation of Trp-P-2 was more than one hundred times less than that of 2-AF. These results suggested that the metabolic activation pathway of these mutagenic heterocyclic amines is different from that of 2-AF. The hamster but not rat cytosol showed the ability to utilize N-hydroxy-2-acetylaminofluorene and 2-acetylaminofluorene as acetyl donor in the N-acetylation of Trp-P-2.

Acetylation↗
PubMed1984

Effect of norharman on DNA strand breaks and mutation of Chinese hamster V79 cells by chemical carcinogens.

The effect of norharman, which shows a comutagenic activity in the Salmonella mutation assay, was examined on the action of mutagens towards Chinese hamster V79 cells. Norharman reduced the DNA strand breaks by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), but enhanced the 4-hydroxyaminoquinoline l-oxide ( 4HAQO )-induced DNA strand breaks. Norharman also reduced the cytotoxicity and the mutagenicity of MNNG but enhanced the cytotoxicity of 4HAQO to V79 cells. In the Salmonella mutation assay, norharman showed no effect on the mutagenic activity of MNNG but reduced the mutagenic activity of 4HAQO . The effect of norharman on the action of mutagens to V79 cells appeared dependent on mutagens and did not correlate with the effect observed in Salmonella mutation assay.

4-Hydroxyaminoquinoline-1-oxide↗
PubMed1984

Neonatal testosterone imprinting of hepatic microsomal drug metabolism and a male-specific form of cytochrome P-450 in the rat.

The effects of neonatal castration and treatment with testosterone on sex-specific forms of cytochrome P-450, namely P-450-male and P-450-female, were studied. Neonatal castration of male rats resulted in a change in the population of forms of cytochrome P-450. Castration 1 day after birth abolished the synthesis of P-450-male and stimulated the synthesis of P-450-female. The decrease in the amount of P-450-male as well as the activities of drug metabolizing enzymes was partially reversed by administration of testosterone after castration.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1984

Effect of morphine on the tissue cyclic AMP and cyclic GMP content in two strains of mice.

The effect of morphine on the cyclic (c) AMP and cyclic (c) GMP concentrations in several organs, and its reversal by naloxone have been investigated in C57BL and DBA strains of mice. Morphine increased the cAMP contents in lungs and muscle, and the cGMP contents in lungs, intestine, heart, liver and muscle in a naloxone-reversible way in C57BL mice only. This is consistent with our previous observation that morphine increased plasma cyclic nucleotide levels in C57BL mice, whereas such an increase was marginal in the DBA strain. These results show that there is a strain difference in the effect of morphine on tissue cyclic nucleotide contents and the possible origin of the plasma cyclic nucleotides which are increased by morphine.

Animals↗
PubMed1984

Predominance of alpha 2-adrenoceptors in porcine thyroid: biochemical and pharmacological correlations.

alpha-Adrenergic agonists such as norepinephrine and clonidine, but not methoxamine, inhibited the increase in cAMP accumulation elicited by TSH in porcine thyroid slices. The inhibitory effect of norepinephrine was abolished by yohimbine but not by prazosin. Likewise, the in vitro release of T4 from the pig thyroid slice stimulated by TSH was inhibited by norepinephrine and the inhibition was antagonized by yohimbine but not by prazosin. These results suggest that the inhibitory effect of alpha-adrenergic agonists is mediated through alpha 2-adrenoceptors. Preincubation of the thyroid slices with islet-activating protein, pertussis toxin, decreased the inhibitory effect of norepinephrine on the cAMP content, suggesting the involvement of guanine nucleotide regulatory protein (Ni) in the inhibition mediated through alpha 2-adrenoceptors. Binding studies with [3H]yohimbine and [3H]prazosin to porcine thyroid membranes revealed the specific and saturable binding of both radioligands. Scatchard analysis of the specific binding revealed a single class of binding sites for each radioligand; however, the maximum number of binding sites for [3H]yohimbine was about 10 times more than that for [3H]prazosin. In accordance with the pharmacological results, binding studies showed a predominance of alpha 2-adrenoceptors in the pig thyroid.

Animals↗
PubMed1984

[Comparative study on the inhibitory effect of glucagon and secretin on the gastroduodenal motility in man].

Manometric study was performed to compare the inhibitory effect of glucagon and secretin on the gastroduodenal motor activity by infused catheter method. The subjects consisted of 3 healthy volunteers and 7 patients with peptic ulcer and other diseases. The following results were obtained. After the intravenous administration of glucagon (1 mg), the motor activity of the stomach and duodenum was inhibited promptly. According to statistic evaluation, the contraction numbers and motility index decreased significantly during 25 minutes compared with the basal values in both stomach and duodenum. After the administration of secretin (100 units), gastric motor activity was markedly inhibited, although duodenal motility increased during 10 minutes due to the initiation of secretin-induced migrating motor complex. The contraction numbers and motility index in stomach decreased significantly during 20 minutes after the administration. The inhibitory effect of glucagon was more remarkable in duodenum than in stomach. On the other hand, secretin was more effective in stomach than in duodenum.

Adult↗
PubMed1984

Glutathione transferase-mediated and non-enzymatic activation and detoxication of the N-hydroxy derivative of Trp-P-2, a potent pyrolysate promutagen.

Glutathione (GSH) transferase-mediated and non-enzymatic activation and detoxication of 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (N-OH-Trp-P-2) were studied in vitro. N-OH-Trp-P-2 is an active metabolite of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), a mutagenic and carcinogenic heterocyclic amine. The enzymatic GSH conjugation with N-OH-Trp-P-2 was catalysed by rat-liver GSH transferase and a rat-liver cytosol fraction to form three conjugates (CH-1, CH-2 and CH-3). The mutagenicities of the GSH conjugates were studied by using Salmonella typhimurium TA98 as the tester strain. The GSH conjugates except for CH-3 were completely detoxicated products, but CH-3 was found to be a more potent mutagen than N-OH-Trp-P-2. The mutagenicity of CH-3 seemed to be due to the direct action of the conjugate, but not to N-OH-Trp-P-2 formed from it.

Animals↗
PubMed1984

Specificity of four forms of cytochrome P-450 in the metabolic activation of several aromatic amines and benzo[a]pyrene.

The involvement of four forms of cytochrome P-450 in the activation of the promutagens, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-6-methyl-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-aminofluorene and 4-aminobiphenyl has been investigated using a Salmonella test system. A high-spin form, P-448 II-a, catalysed the activation of IQ and Glu-P-1 28 and 12 times faster, respectively, than a low-spin form, P-448 II-d, whereas benzo[a]pyrene was metabolized to the phenols 60 times faster by P-448 II-d than P-448 II-a. Both P-448 II-a and P-448 II-d were highly active in the activation of Trp-P-2 and 2-aminofluorene. Treatment of CDF1 mice with polychlorinated biphenyls (PCB) increased the microsomal-activating ability for the promutagens in various degrees. More than a ten-fold increase was observed with Trp-P-2, while the increase was only two-fold with IQ. No sex-related difference was observed for the hepatic microsomal activating ability of male and female CDF1 mice for Trp-P-2, Glu-P-1 or IQ. These results indicate that more than two forms of cytochrome P-450, which are inducible by treatment with PCB or 3-methylcholanthrene, mediate the metabolic activation of heteroaromatic amines in rats and mice.

Amines↗
PubMed1984

Development of tolerance to alpha-2 adrenergic agonists in the vascular system of the rat after chronic treatment with clonidine.

The possibility of development of tolerance after chronic treatment with clonidine (CLN) was investigated in the vascular system of the rat. Rats were treated with CLN for 3 to 10 days by dissolving the drug in the drinking water at concentrations of 0.1 to 10 micrograms/ml. Pressor responses to several vasoconstrictors were examined after pithing. Rats given CLN-containing water at a concentration of 10 micrograms/ml were considered as receiving CLN at about 1 mg/kg/day and were found to be subsensitive to l-norepinephrine. Decrease in the sensitivity varied with the length of CLN treatment and the maximum decrease was attained within 5 days of the treatment. Recovery from the subsensitivity required a long deprivation time of CLN; after 10 days of treatment, 14 days of deprivation did not cause any recovery in the sensitivity. The subsensitivity also was observed in the alpha-2 adrenergic agonists, CLN and azepexole, whereas it was not detected in alpha-1 adrenergic agents, phenylephrine and methoxamine, and the nonadrenergic vasoconstrictors, angiotensin-II and Lys-vasopressin. Pressor responses to stimulation of the complete sympathetic outflow also decreased in the CLN-treated rats. These results show clearly that chronic treatment with CLN makes rat vasculature subsensitive to l-norepinephrine and suggest that this phenomenon involves specific desensitization developed in the contractile mechanisms of vascular smooth muscles mediated by alpha-2 adrenergic receptors.

Adrenergic alpha-Agonists↗