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Biomedical subjects

R Kato

Publications and source records attributed to R Kato.

At least 667 records · Page 37Linked to original sources
PubMed1980

Isolation and characterization of active metabolites of tryptophan-pyrolysate mutagen, TRP-P-2, formed by rat liver microsomes.

The mutagenic compound derived from the pyrolysis of tryptophan, 3-amino-1-methyl-5H-pyrido-[4,3b]indole (Trp-P-2) was metabolized by rat liver microsomes to more than four metabolites, separable by high performance liquid chromatography. Among these metabolites, two metabolites, M-3 and M-4 were directly active in increasing the frequency of mutation in Salmonella typhimurium TA98. Treatments of rats with polychlorinated biphenyl (PCB) or 3-methylcholanthrene dramatically induced the activity of liver microsomes to form these active metabolites, while treatment with phenobarbital was without effect. A major active metabolite (M-3) formed the pentacyano-ammine ferroate, which is known to be formed by reaction of sodium pentacyano-ammine ferroate with some hydroxylamines. Further this metabolite was oxidized to the minor active metabolite (M-4) with potassium ferricyanide or gamma-manganese dioxide, and was reduced back to Trp-P-2 with titanium trichloride. These results indicated that the major active metabolite of Trp-P-2, which is formed by cytochrome P-450, is the 3-hydroxyamino derivative.

Animals↗
PubMed1980

Metabolic activation of mutagenic tryptophan pyrolysis products (Trp-P-1 and Trp-P-2) by a purified cytochrome P-450-dependent monooxygenase system.

Tryptophan pyrolysis products, Trp-P-1 and Trp-P-2, were activated to metabolites mutagenic to Salmonella typhimurium by cotychorome P-450 purified from rat liver microsomes. Of the four purified cytochrome P-450 preparations tested, PCB P-448 and MC P-448 showed high activity, while PCB P-450 and PB P-450 were less active. The number of revertants was proportional to the amount of cytochrome PCB P-448 added under the conditions used.

Animals↗
PubMed1980

Effects of alpha- and beta-adrenergic blockers on chlorpromazine-induced elevation of plasma glucose and cyclic AMP in fed mice.

The subcutaneous administration of chlorpromazine (CPZ) caused a dose response increase in plasma glucose and cyclic AMP levels in fed male mice. Hexamethonium abolished the elevation of both plasma glucose and cyclic AMP. Propranolol did not inhibit the elevation of plasma glucose but inhibited the increase of plasma cyclic AMP. In contrast, phentolamine and yohimbine completely suppressed the elevation of plasma glucose but not that of plasma cyclic AMP. These results indicate that the hyperglycemia due to CPZ was mediated through the stimulation of alpha-adrenoceptor and on the contrary CPZ increased plasma cyclic AMP through the stimulation of beta-adrenoceptor and that the increase in plasma glucose induced by CPZ was independent of the activation of adenylate cyclase and the increased plasma cyclic AMP. In addition, in contrast to phentolamine and yohimbine, phenoxybenzamine was ineffective to prevent the hyperglycemia induced by CPZ. Moreover, a higher dose of dihydroergotamine was required to inhibit the hyperglycemia.

Adrenergic alpha-Antagonists↗
PubMed1980

Inhibition by SKF 525-A of 7-ethoxycoumarin O-deethylation in microsomal and the reconstituted monooxygenase systems from PCB-treated rat livers.

Addition of diethylaminoethyl 2,2-diphenylvalerate-HCl (SKF 525-A) to the incubation mixture containing liver microsomes or purified cytochrome P-450 (PCB P-450) from PCB (KC-500)-treated rats resulted in non-competitive inhibition of 7-ethoxycoumarin O-deethylation activity whereas the addition to the incubation mixture containing purified cytochrome P-448 (PCB P-448) showed a competitive inhibition. Fortification of PCB-induced microsomes with purified NADPH-cytochrome P-450 reductase enhanced the O-deethylation activity. With the reductase-fortified microsomes, SKF 525-A inhibited the O-deethylation in a competitive manner. Based on these results, we confirmed that SKF 525-A inhibits non-competitively and competitively, depending on the species of cytochrome P-450. Our results also support the view that in microsomes from PCB-treated rats, PCB P-450 rather than PCB P-448 is mainly involved in the O-deethylation reaction, presumably due to the presence of a limited amount of NADPH-cytochrome P-450 reductase in microsomes.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1980

Effect of morphine on the release of thyroid-stimulating hormone stimulated by exposure to cold, thyroidectomy and the administration of thyrotrophin releasing hormone in male rats.

Morphine reduced the release of thyroid-stimulating hormone (TSH) which stimulated by exposure to cold and by thyroidectomy as well as reducing the basal level of TSH in the serum of male rats. Thi inhibitory effect of morphine was antagonized by naloxone which did not enhance the basal or cold-induced TSH release. Pretreatment with morphine did not reduce the release of TSH induced by exogenous thyrotrophin-releasing hormone (TRH) but enhanced it. This effect of morphine was also antagonized by naloxone. The above results suggested that the effect of morphine in reducing levels of serum TSH was not mediated by blocking the effect of TRH on the anterior pituitary gland, but that it was probably mediated by the inhibition of the release of TRH.

Animals↗
PubMed1980

Adrenergic regulation of blood glucose levels: possible involvement of postsynaptic alpha-2 type adrenergic receptors regulating insulin release.

We have demonstrated that while phenoxybenzamine and prazosin (10(-7)-10(-4) mol/kg i.p.) are ineffective in inhibiting the hyperglycemia induced by alpha adrenergic agonists in fed male mice, phentolamine, yohimbine and dihydroergotamine are effective. These results suggest the involvement of alpha-2 type adrenergic receptors in the regulation of the plasma glucose levels. When attempting to elucidate the mechanism of such differences, we found that the release of immunoreactive insulin induced by epinephrine was markedly stimulated by phentolamine, yohimbine and dihydroergotamine, whereas phenoxybenzamine and prazosin had little effect. The ineffectiveness of these two compounds to inhibit the hyperglycemia induced by alpha adrenergic agonists indicates that the postsynaptic alpha adrenergic receptors which suppress the secretion of immunoreactive insulin from B cells of pancreatic islets are not blocked and that the alpha adrenergic receptors which control immunoreactive insulin secretion differ from the classical postsynaptic alpha adrenergic receptors and more closely resemble presynaptic alpha-2 adrenergic receptors.

Adrenergic alpha-Antagonists↗
PubMed1980

Metabolic activation of mutagenic tryptophan pyrolysis products by rat liver microsomes.

In an attempt to determine whether cytochrome P-450 metabolizes tryptophan pyrolysis products, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) to active forms, studies were done using microsomes and the 9000 x g supernatant (S-9) from polychlorinated biphenyl mixture-treated rat livers together with Salmonella typhimurium TA 98 as a tester strain. The number of revertants increased with increments in the amount of S-9 fraction added. The highest mutation was seen with an amount of S-9 that is equivalent to 2.5 mg of liver tissue; however, further increase in the S-9 fraction resulted in a sharp decline in the number of revertants. There was a similar biphasic response when a relatively large amount of S-9 fraction was incubated for an increasing length of time. Microsomes showed parallel biphasic responses, and, in addition, the 105,000 x g supernatant fraction was ineffective in increasing the number of revertants. These results suggested that most if not all of the ability of the S-9 fraction to convert Trp-1 and Trp-P-2 to active forms resided in the microsomes. The involvement of microsomal cytochrome P-450 in this process was further confirmed by the following evidence. The treatment of rats with polychlorinated biphenyl mixture and 3-methylcholanthrene resulted in a marked increase in the ability of microsomes to activate Trp-P-1 and Trp-P-2, and the activation reaction required reduced nicotinamide adenine dinucleotide phosphate as a cofactor and was inhibited by carbon monoxide, 7,8-benzoflavone, n-octylamine, and 2-diethylaminoethyl-2,2-diphenylvalerate. The mutagenic metabolite formed as a result of microsomal metabolism of Trp-P-2 was fairly stable and survived heating at 90 degrees for 7 min. With a high-performance liquid chromatography, an active metabolite of Trp-P-2 was purified. A preliminary analysis showed this molecule to be an N-hydroxylated derivative of Trp-P-2.

Animals↗
PubMed1980

Suppressive effect of morphine on serum gonadotropin levels in castrated rats.

A single administration of morphine reduced both serum LH and FSH levels in castrated Wistar rats. As the inhibitory effect of morphine on serum LH was antagonized by naloxone, the opiate receptors are involved. Decrease in the serum FSH levels induced by morphine was considerably less than the decrease in serum LH, and naloxone did not significantly reverse this effect of morphine on serum FSH. Increase in the serum LH induced by exogenous LHRH was slightly potentiated and not inhibited by a large dose of morphine, in both intact and castrated rats. Increase in the serum FSH in intact male rats induced by exogenous LHRH was not altered by morphine. In the castrated animals, exogenous LHRH did not further increase the serum FSH levels and the latter was not altered by a concomitant administration of morphine. These results clearly show that the decrease in serum gonadotropin levels by morphine is not due to inhibition of the stimulatory effect of LHRH on the pituitary gland. The mechanism of the differential suppression on serum LH and FSH by morphine is postulated.

Animals↗
PubMed1980

Disposition and enterohepatic circulation of diclofenac in dogs.

Following i.v. administration of 14C-labelled 2-(2',6'-dichloroanilino) phenylacetic acid (14C-diclofenac) (25 mg/kg) to dogs, 65% of the dose of total radioactivity was excreted in the bile in the first 6 h. A trace of unchanged diclofenac and three metabolites were demonstrated in the bile by 2-dimensional TLC. Two of these metabolites were identified as diclofenac acyl-glucuronide (80% of total radioactivity in the bile) and taurine conjugate (10%); the third was an unknown metabolite (2%). Diclofenac acyl-glucuronide was hydrolyzed by weak alkaline and beta-glucuronidase. Intraduodenally administered diclofenac acyl-glucuronide was absorbed, and then excreted in the bile again. This suggests that diclofenac acyl-glucuronide is hydrolyzed in the intestine, and undergoes enterohepatic circulation. The plasma half-life of diclofenac was 1.3 h in dogs.

Animals↗
PubMed1979

Inhibition by cholinergic agonists of the prolactin release induced by morphine.

The cholinergic agonists, pilocarpine, physostigmine and nicotine, inhibited the prolactin release induced by morphine in male rats in vivo. Pilocarpine also inhibited the release of prolactin induced by beta-endorphin or metoclopramide without affecting the basal and haloperidol-stimulated serum prolactin levels. The inhibitory effect of pilocarpine on the morphine-stimulated release of prolactin was antagonized by concurrent administration of atropine but not by atropine methylnitrate or by mecamylamine, while the inhibition by nicotine was antagonized by mecanylamine but not by atropine. The stimulation of prolactin release by morphine and its reversal by pilocarpine were observed after the administration of haloperidol or alpha-methyltyrosine. These results suggest that the central cholinergic system exertes an inhibitory influence on the prolactin release induced by morphine or beta-endorphin and the cholinergic inhibition is not mediated via catecholaminergic neurons.

Animals↗
PubMed1979

Effect of narcotic analgesics and naloxone on proestrous surges of LH, FSH and prolactin in rats.

Morphine (50 mg/kg), given at 12:00 h and 14:00 h to proestrous rats, completely inhibited the proestrous surges of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (Prl). However, when it was given at 16:00 h, the inhibitory effect of morphine (Mor) was decreased. Pethidine and nalorphine inhibited the proestrous surges, while pentazocine showed a weaker inhibitory effect. Naloxone (Nx), given simultaneously or 2 h after morphine (Mor), at 1/20 the dose of Mor, inhibited the blockade of the proestrous gonadotropin release exerted by Mor, while the onset of the surges was delayed when it was given 3 h after Mor.

Analgesics, Opioid↗