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Biomedical subjects

T Komoda

Publications and source records attributed to T Komoda.

At least 127 records · Page 7Linked to original sources
PubMed1987

Certain neuroleptics reduce bone mineralization in schizophrenic patients.

A significant increase of urinary Ca and hydroxyproline levels and a decrease of urinary alkaline phosphatase activity were found in 12 schizophrenic patients receiving certain neuroleptic drugs. In these patients, the levels of active metabolites of vitamin D3 were decreased, while the levels of midmolecule parathyroid hormone were within the normal range, except for 2 cases. These results suggest that certain neuroleptics induce the increased urinary Ca excretion through suppression of active vitamin D3 formation and that chronic treatment with certain neuroleptics may induce abnormal bone mineralization.

Adolescent↗
PubMed1986

A possible mechanism of induction and translocation into blood stream of rat alkaline phosphatase activity by bile duct ligation.

We investigated the effects of bile duct ligation on alkaline phosphatase (ALP) activities in liver, calvarium, duodenum, and ileum in rats and its possible mechanism of action. ALP isozyme activities in the ligated rats were significantly elevated in the liver and duodenum, while those in the ileum and calvarium were markedly decreased. The ALP isozyme activity elevated by the ligation was obviously suppressed by prior administration of indomethacin, an inhibitor of prostaglandin synthesis. Moreover, phorbol ester also elevated the ALP activity as well as the phosphatase level in the ligated rat. However, other drugs, such as an inhibitor of protein kinase C and calmodulin, showed different effects: calmodulin stimulated an 11.0-, 1.3-, or 1.5-fold increase in ALP activity in the ileum, duodenum, or calvarium, respectively; whereas the hepatic enzyme activity was not affected. The induction by calmodulin was markedly different from that by the ligation. Moreover, imipramine, an inhibitor of protein kinase C, had little effect. These results suggest that prostaglandin is a possible ALP inducer in ligated rats, probably working by elevating the cAMP level. On the other hand, the ligation induced simultaneously de novo synthesis of the membranous and soluble ALP isozymes; and the release rate of the soluble enzyme was greater than that of the membranous isozymes, indicating that the soluble enzyme might be a main source of the induced serum ALP. Lectin affinity chromatography indicated that the soluble enzyme or induced serum enzyme may contain more fucose than that of the membranous one, suggesting that the sugar moiety in the ALP molecule may relate to the clearance of ALP from or its release into the circulation.

Alkaline Phosphatase↗
PubMed1986

Different lectin affinities in rat alkaline phosphatase isozymes: multiple forms of the isozyme isolated by heterogeneities of sugar moieties.

Differences among rat alkaline phosphatases from various organs were established by using the serial lectin affinity technique. Elution profiles of isozymes with various lectin columns were significantly different from each other, and it was possible to distinguish between isozymes by this technique. It has been shown by many workers that a high-mannose-type and/or hybrid-type sugar chain is contained in the fraction bound strongly to concanavalin A-Sepharose. The duodenal alkaline phosphatase had a low content of this fraction, although the content of this fraction obtained from duodenal explants was increased markedly when explants were cultured with swainsonine, which is an inhibitor of alpha-mannosidase II, and this leads to the accumulation of high-mannose-type and hybrid-type sugar chains in the pathway of sugar chain processing. From the present results, it is suggested that differences in the elution profiles of isozymes may be due to the structural differences of sugar chains in alkaline phosphatases.

Alkaline Phosphatase↗
PubMed1986

Ontogenic and phylogenic studies of intestinal, hepatic, and placental alkaline phosphatases. Evidence that intestinal alkaline phosphatase is a late evolutionary development.

We have studied the intrauterine development of guinea pig and rat organ phosphatases using biochemical, immunologic, and histologic techniques. In all organs tested the features of the adult phosphatase activity were achieved during the second or third gestational phases. In the rat, the tissue-unspecific phosphatase activity was found by immunoprecipitation with antiserum to rat liver phosphatase in all gestational phases in liver and placenta. The high liver activity in the first phase of gestation corresponded to hematopoietic cells. Hepatocyte phosphatase did not appear until the second gestational phase. The tissue-unspecific phosphatase activity was found in the first and second gestational phase in surface intestinal epithelial cells, even after crypt formation occurred. Once phosphatase appeared in enterocytes on villi, only the intestinal-type enzyme was detected. Alkaline phosphatase was measured in the liver and intestine from animals in various phyla. In fish and reptiles, the intestinal activity had the enzymatic characteristics of the tissue-unspecific enzyme. The appearance of intestinal alkaline phosphatase with unique properties and high specific activity is a characteristic of mammals.

Alkaline Phosphatase↗
PubMed1985

Inhibitory effect of phenothiazine derivatives on bone in vivo and osteoblastic cells in vitro.

We tested the inhibitory effects of phenothiazine derivatives on bone in vivo and osteoblastic cells in vitro. Chlorpromazine (CPZ) and trifluoperazine (TFPZ) dose-dependently decreased alkaline phosphatase activity in calvariae of rats: half-maximal inhibitory effects of CPZ and TFPZ were at 2.0 and 4.0 mg/kg, respectively. These effects were more specific for calvaria and ileum than for liver and duodenum. CPZ inhibited the proliferation of osteoblastic clone MC3T3-E1 cells to a greater extent than that of liver epithelial clone RLC-18(4) cells in vitro. CPZ, TFPZ and perphenazine (PNZ) also affected rather specifically alkaline phosphatase activity and collagen synthesis and were not cytotoxic. These in vivo and in vitro findings suggest inhibitory effects on osteoblastic cell function(s). However, promethazine (PMZ) had little effect in vivo and in vitro. In addition, increases in serum calcium and phosphate induced by CPZ indicate its possible involvement in bone resorption.

Alkaline Phosphatase↗
PubMed1984

Induction of rat hepatic and intestinal alkaline phosphatase activity produced by bile from bile duct-ligated animals.

Bile duct ligation caused a threefold elevation of not only hepatic but also intestinal alkaline phosphatase. The increase was transient in intestinal mucosa and peaked at 12 h. Hepatic phosphatase levels reached a plateau by 36 h. Intraperitoneal injection of bile from ligated animals into normal rats produced qualitatively similar results. Studies were performed to further characterize the induction of phosphatase activity in both tissues. The addition of bile from ligated animals to organ explants of liver and intestine produced a two- and threefold rise in activity, respectively. Therefore, neural and hormonal factors are not essential in producing this induction. The increased activity produced in vitro in both tissues was due to heat-stable and dialyzable factor(s) and was blocked by inhibitors of protein synthesis. In the intestine activity occurred over the entire brush border as demonstrated by electron microscopic histochemistry. In the liver, increased activity was noted over the entire plasma membrane and was not localized to the canalicular membrane. Tunicamycin treatment of liver and intestinal explants markedly suppressed the induced phosphatase activity. Simultaneous treatment with protease inhibitors restored some of the phosphatase activity. These findings suggest that glycosylation of the alkaline phosphatase might provide at least partial protection from proteolysis.

Alkaline Phosphatase↗
PubMed1983

A possible mechanism for the changes in hepatic and intestinal alkaline phosphatase activities in bile-duct-ligated rats or guinea pigs.

The effects of bile-duct ligation on hepatic and intestinal (jejunum) alkaline phosphatase activities were studied using rats and guinea pigs. In ligated rats, the enzyme activity was increased 4.1-fold in the liver after 24 h and 2.8-fold in the intestine after 12 h. In guinea pigs, the hepatic and intestinal enzyme activities were increased 2.3-fold and 1.5-fold after 100 and 24 h, respectively. The intestinal activity was induced sooner after ligation than hepatic activity. The induction of alkaline phosphatase was inhibited by prior treatment of animals with amanitin, an inhibitor of RNA polymerase activity. This result indicates that the induction is associated with de novo enzyme synthesis. The content of cyclic AMP in liver and intestine increased immediately after ligation. The increase in alkaline phosphatase activities was also inhibited by pretreatment with chlorpromazine, an inhibitor of adenylate cyclase activity. Hence, cellular cyclic AMP may be implicated in playing a role in the induction of alkaline phosphatase by bile-duct ligation.

Alkaline Phosphatase↗