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Biomedical subjects

H Kitagawa

Publications and source records attributed to H Kitagawa.

At least 631 records · Page 35Linked to original sources
PubMed1978

Effects of magnesium on contractile responses induced by electrical transmural stimulation and noradrenaline in rabbit thoracic aorta.

1 In rabbit isolated thoracic aortae, effects of magnesium ions on the contraction and (3)H-efflux in response to electrical transmural stimulation and on the contractile responses induced by noradrenaline and KCl were investigated.2 Addition of magnesium (1.2, 3.6, 12.0 and 24.0 mM) to the bathing solution inhibited the electrically induced contractions in a dose-related manner; the inhibition was complete with a concentration of 24.0 mM.3 The increase in (3)H-efflux induced by electrical transmural stimulation was inhibited by the addition of magnesium to the superfusing fluid, but a complete block was not obtained even in high concentrations of magnesium.4 Magnesium ions (1.2, 3.6, 12.0 and 24.0 mM) inhibited the contractile responses induced by low concentrations of noradrenaline (2 x 10(-8)M) and KCl (2 x 10(-2)M). However, the responses induced by higher concentrations of noradrenaline (5 x 10(-7) and 10(-5)M) and KCl (3 and 4 x 10(-2)M) were enhanced by low concentrations of magnesium.5 Magnesium ions affect both presynaptic and effector sites in rabbit thoracic aortae but in a different manner; magnesium manifests only an inhibitory effect on noradrenaline release from the adrenergic nerves, but dual effects on reactivity of vascular smooth muscle, depending on concentrations of magnesium and stimulants; it is suggested that the change in vascular reactivity is more important than the reduction in transmitter release when magnesium inhibits the response to nerve stimulation.

Animals↗
PubMed1978

Enhancement in vivo of drug oxidations following administration of benzphetamine, acetone, metyrapone and dimethylsulfoxide.

Effects of benzphetamine, acetone, metyrapone and dimethylsulfoxide administration to rats on the metabolism of drugs by liver 9,000 x g supernatant fraction were studied herein. Activities for aniline hydroxylation and phenacetin O-deethylation were increased while ethylmorphine and benzphetamine N-demethylations were unchanged by the single administration of acetone, metyrapone or dimethylsulfoxide. Increase in aniline hydroxylase activity by about 53.4% and in phenacetin O-deethylase activity by about 44.4% were observed at 30 min after the single administration of benzphetamine whereas ethylmorphine N-demethylase activity was slightly decreased. NADPH-cytochrome P-450 reductase activity and cytochrome P-450 content were unaltered until 12 hr after the single administration of benzphetamine. Aniline hydroxylation was increased by the addition of benzphetamine to the incubation mixture and the increase in aniline hydroxylation caused by benzphetamine could be reversed by washing the microsomes.

Acetone↗
PubMed1978

Influence of tracheal muscular tone on the initiation of cough reflex.

We devised a canine blood-perfusion preparation which made feasible administration of drugs directly at the local tracheal site. The hypothesis of Salem and Aviado on cough mechanism that a local airway constriction induced by stimuli may be a trigger in stimulating cough receptors was investigated using this preparation. Close intraarterial injections of acetylcholine (ACh) and histamine did not elicit a cough although intense tracheal constrictions were evident. The cough reflex elicited by electrical stimulation of the mucosa of isolated upper trachea in situ was accompanied by a slight systemic hypotension, tracheal vasodilatation and tracheal muscular constriction. The latter two changes occurred after a time lag following coughs. Close intraarterial infusions of isoproterenol and papaverine caused a prominent tracheal dilatation, but did not suppress the coughs. Pretreatment with atropine sufficiently inhibited cholinergic tracheoconstriction but had no effect on the electrically induced coughs. Furthermore, an augmentation of the tracheal muscular tone produced by an infusion of ACh did not enhance the cough reflex. In light of our observations, the aforementioned hypothesis should be reconsidered.

Acetylcholine↗
PubMed1978

Comparison of effects of acetaminophen on liver microsomal drug metabolism and lipid peroxidation in rats and mice.

Studies were conducted to determine the in vivo effect of acetaminophen (AAP) on the lipid peroxidation, drug metabolizing enzyme activity and microsomal electron transfer system of rat and mouse liver. AAP was found to inhibit ethylmorphine N-demethylase activity in the presence of NADPH and this inhibition of the enzyme was due to decrease in cytochrome P-450 content, but not due to change in lipid peroxidation in liver microsomes. Kinetical data showed that AAP administration had no effect on Km values of ethylmorphine N-demethylase, however, a decrease in the Vmax values was seen in rats and mice. There was no significant effect of AAP on both NADPH-cytochrome c reductase and the content of cytochrome b5 3 hours after this administration to rats and mice. On the other hand, AAP induced a significant decrease in NADH-ferricyanide reductase in mice, but not in rats. The greatest decrease in cytochrome P-450 observed among the components of the liver microsomal electron transfer system of rats and mice.

Acetaminophen↗
PubMed1978

Glutathione depletion by aniline analogs in vitro associated with liver microsomal cytochrome P-450.

Enzymic depletion of glutathione (GSH) in vitro by aniline analogs was mostly dependent on the cytochrome P-450 level in liver microsomes. In a case of acetaminophen (AAP), active metabolite of AAP formed through liver microsomal drug metabolizing enzymes consumed GSH. The active metabolite formed binds, at least in part, covalently to liver microsomal proteins. In addition, species differences in the extent of GSH depletion by AAP in vitro was related to the amounts of the active metabolite of AAP bound covalently to liver microsomal protein(s) by experiments using 14C-AAP. Similar depletion of GSH was also seen with other aniline analogs such as aniline itself and p-chloroaniline, but not with acetanilide, in four animal species. These in vitro results obtained here strongly support the well-known findings concerning both GSH depletion and covalent binding in vivo of the active metabolite after AAP treatment.

Acetaminophen↗
PubMed1978

Lipid peroxidation activity mediated by NADPH-cytochrome C reductase purified from rabbit liver microsomes.

Purified NADPH-cytochrome c reductase of rabbit liver microsomes was examined to determine whether or not the reported low lipid peroxidation activity of rabbit liver microsomes is due to the enzyme, NADPH-cytochrome c reductase. NADPH-cytochrome c reductase was purified from phenobarbital-treated rabbit liver microsomes to a specific activity of 14.9 to 21.4 unit per mg of protein with a yield of 15.2 to 16.4%. The purified sample (21.4 unit/mg of protein) was almost homogenous as determined by sodium dodecylsulfate gel electrophoresis. This sample was used for determining lipid peroxidation activity. EDTA and ferrous ion but not ADP were essential requirements for the activity. FMN enhanced the activity when low concentrations of the NADPH-cytochrome c reductase were used for the assay. NADP and 2'-AMP, which are inhibitors of NADPH-cytochrome c reductase, inhibited the lipid peroxidation activity. a-Tocopherol and p-chloromercuribenzoate (PCMB) also inhibited the activity. From these results, we confirmed the rabbit liver microsomal enzyme NADPH-cytochrome c reductase plays a role in lipid peroxidation activity. The reported low lipid peroxidation activity in rabbit liver microsomes does not appear to be caused by the NADPH-cytochrome c reductase.

4-Chloromercuribenzenesulfonate↗
PubMed1978

Effects of various compounds on lipid peroxidation mediated by detergent-solubilized rat liver NADPH-cytochrome C reductase.

A reconstituted lipid peroxidation system containing NADPH-cytochrome c reductase isolated from detergent-solubilized rat liver microsomes was used to determine the effects of several compounds, including drugs, on the lipid peroxidation activity. EDTA and ferrous ion were essential requirements for reconstitution of the activity. The addition of 1,10-phenanthroline to the system containing both EDTA and ferrous ion further enhanced the activity. Pyrocatecol, thymol, p-aminophenol, imipramine, p-chloromercuribenzoate (PCMB) and alpha-tocopherol exhibited strong inhibition, aniline, N-monomethylaniline, aminopyrine, benzphetamine, SKF 525-A and NADP exhibited moderate inhibition, and phenol, benzoic acid, acetanilide and nicotinamide exhibited less or no inhibition at the concentrations lower than 1000 micron M. Metal ions such as Hg+, Hg2+, Co2+, Cu2+, Mn2+ and U6+ inhibited lipid peroxidation strongly. In addition, Cd2+, St2+ and Ca2+ exhibited less potent to moderate inhibition, and Ba2+ and Mg2+ were without effects on the activity. Among sulfhydryl compounds tested, dithiothreitol inhibited lipid peroxidation to a greater extent than did the other three compounds, glutathione, cysteine and mercaptoethanol.

Amines↗
PubMed1978

Antiulcerogenic effect of a pyrido-benzodiazepine derivative (L-S 519) on experimental ulcers.

Effects of a tricyclic, pyrido-benzodiazepnie derivative, 5,11-dihydro-11-[(4-methyl-1-piperazinyl)acetyl]-6H-pyrido[2,3-6][1,4]-benzodiazepin-6-one-dihydrochloride (L-S 519) on experimental ulcers produced by pylorus ligation, cold restraint-stress, and reserpine, and on gastric secretions stimulated by histamine, tetragastrin and carbachol in rats were studied. L-S 519 was half as potent as atropine in preventing these experimental acute ulcers and in decreasing the spontaneous gastric secretion. This compound inhibited to various degrees the gastric secretion stimulated by histamine, tetragastrin and carbachol in acute fistula rats. On the other hand, the antimuscarinic effects of L-S 519 were much weaker than those of atropine in both in vivo and in vitro experiments. Furthermore, the antigastric secretory effect of L-S 519 was observed even in pylorus-ligated, vagotomized rats. By contrast, the effect of L-S 519 was reduced by pretreatment with 6-hydroxydopamine. These results suggest that the adrenergic mechanisms, in addition to a weak antimuscarinic property, are involved in antisecretory and antiulcerogenic effects of L-S 519.

Animals↗
PubMed1978

Anticancer activity of isomers of 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole.

Three phenylimidazothiazole isomers, L-(-)-form (levamisole), D-(+)-form (dexamisole), and DL-(+/-)-form (tetramisole), modulate mouse and rat immune responsiveness. They depress the relapse of urinary bladder cancer, BC-47, when they are used with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for treatment of rats bearing BC-47. Levamisole was the most effective isomer. Effectiveness of the isomers is expressed by their ability to enhance the number of plaque-forming cells to sheep red blood cells. They also stimulate the DNA synthesis of murine lymphocytes in vitro.

Animals↗
PubMed1978

Effect of chemotherapeutic agents on the growth of rat bladder cancer, BC-47.

Effect of clinically available chemotherapeutic agents on transplantable and tissue culture bladder carcinoma cell line, BC-47, which were syngeneic to host animals, was confirmed. Adriamycin, vincristine, and bleomycin possessed predominant antitumor activity. 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) also reduced the tumor load of the host after which the tumor began to grow at the site of inoculation. Alkylating agents such as nitrogen mustard N-oxide (Nitromin), cyclophosphamide, 3,3'-dimesyloxydipropylamine tosylate (864T), and mitomycin-C possessed a weak activity, while antimetabolites such as 5-fluorouracil, 1-(1'=furyl)-5-fluorouracil (FT-207), cytosine arabinoside, and behenoylcytosine arabinoside possessed no activity.

Animals↗