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Biomedical subjects

M Katori

Publications and source records attributed to M Katori.

At least 127 records · Page 7Linked to original sources
PubMed1989

[Pharmacology of prostaglandins; their profile and characterization in the body].

Arachidonic acid metabolites, prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), are classified as a type of autacoids. They are not stored in the cells, but stored as a precursor acid, arachidonic acid, in membrane phospholipids. Various physiological stimuli activate phospholipase A2 and release arachidonic acid, which is converted to 1 or 2 products by related enzymes within a few minutes, depending upon individual cell functions. The metabolites are readily inactivated in aqueous solution and in the body. The structures of the various metabolites are quite similar, but their pharmacological actions vary from metabolite to metabolite and some exert opposite actions to those of others. The metabolites play some pivotal roles in physiological or pathophysiological responses such as pain sensation, fever, plasma leakage and skin erythema. Thus, non-steroidal anti-inflammatory drugs, like aspirin, exert their actions through cyclooxygenase inhibition at low doses. PGE2 can be detected in the exudate of acute inflammatory models, and the simultaneous release of PGE2 with bradykinin induces a large increase in plasma leakage and triggers exudate accumulation. LTB4 induces extravasation of PMN leukocytes at the microcirculatory level and is generated in the reperfused area of infarcted cardiac tissue after ligation of rat coronary artery, but in the latter case, the leukocyte migration was not solely induced by LTB4, which was replaced by a complement component (C5a). LTC4 may be involved in ethanol injury of the gastric mucosa and endogenous PGE2 prevents this injury. The real roles of individual arachidonic acid metabolites have been gradually disclosed, but most of the roles are still yet to be clarified.

Animals↗
PubMed1989

Biphasic accumulation of leukocytes in rat cardiac infarct tissue caused by leukotriene B4 and complement.

An initial increase (3-12 hr) in the polymorphonuclear leukocytes (PMN) counts after ligation of the rat left main coronary artery was reduced by 49.4% (at 12 hr) by a 5-lipoxygenase inhibitor, AA-861 (80 mg/kg, p.o., 1 hr before ligation). Depletion of the complement components induced by cobra venoma factor (CVF) (i.v.), given one day before, resulted in significant reduction in the PMN accumulation after 12 hr (by 63.6% at 24 hr). The combined treatment (CVF+AA-861) suppressed the PMN accumulation by 69.7% (24 hr). The infarct size at 48 hr was also reduced by approximately 36% by either AA-861, CVF or combined treatments.

Animals↗
PubMed1988

Time course analyses of kinins and other mediators in plasma exudation of rat kaolin-induced pleurisy.

Pleurisy was induced in rats by an intrapleural injection of 0.5 ml of 1% kaolin. The exudation of plasma into the pleural cavity showed two peaks at 20 min and 3-5 h after the kaolin injection. The volume of the pleural fluid increased gradually up to 5 h. The effects of treatment with mepyramine, methysergide, captopril, bromelain and indomethacin suggested that the early phase (20 min) of exudation was mediated mainly by kinins, histamine and 5-HT, and that the late phase (3 h) was mediated by prostaglandins (PGs) and possibly kinins. We measured the levels of histamine, kinin and PG in the pleural exudate to verify the involvement of the mediators mentioned above. Intracellular histamine levels decreased markedly and extracellular histamine levels increased significantly 20 min after the induction of kaolin pleurisy. Only threshold levels of kinin were detected after the induction of pleurisy. Captopril treatment, however, increased kinin levels which peaked at 20 min and decreased rapidly thereafter. Levels of 6-keto-PGF1 alpha and thromboxane B2 showed a peak at 20 min, whereas levels of PGE2 increased gradually from 20 min to 5 h. These results indicate that kaolin-induced pleurisy is a kinin-related inflammation and could be used as a model for studying the in vivo interaction of the kallikrein-kinin system and PGs at inflammatory sites.

Animals↗
PubMed1988

Dimethylisopropylsilyl ether derivatives in gas chromatography-mass spectrometry of some prostanoids. Application to the microdetermination of 15-ketoprostaglandin F2 alpha formed by enzymatic conversion of PGF2 alpha in vitro.

Treatment of 15-ketoprostaglandin F2 alpha (15-keto-PGF2 alpha) with ethereal diazomethane at -78 degrees C provided only the expected methyl ester (ME), without the formation of the pyrazoline adduct. The electron-ionization mass spectrum of the dimethylisopropylsilyl (DMiPS) ether derivative of 15-keto-PGF2 alpha ME showed the molecular ion, and the characteristic fragment ion of [M-43]+ was of high abundance. The appearance of these ions in the high-mass region made it possible to determine trace amounts of 15-keto-PGF2 alpha in biological specimens without any interference from endogenous substances. The detection limit for the DMiPS ether derivatives of 15-keto-PGF2 alpha ME was 12 pg (signal-to-noise ratio = 10). The method was applied to the analysis of 15-keto-PGF2 alpha obtained by the enzymatic conversion of PGF2 alpha with 15-hydroxyprostaglandin dehydrogenase in vitro.

Dinoprost↗
PubMed1988

Detection of leukotriene B4 in cardiac tissue and its role in infarct extension through leucocyte migration.

The main left coronary artery of rats was ligated near its origin under light ether anaesthesia and the infarction observed for 48 h. The ischaemic area was determined after an intravenous injection of pontamine sky blue dye 1 h before induction of cardiac arrest with potassium chloride. The unstained area (true ischaemic area) decreased with time to 27.1% of the left ventricle at 48 h, whereas the intensely stained area between the normal and the true ischaemic areas increased with time, suggesting that blood was flowing to the border from the normal surrounding tissue. The infarcted area, identified by its lack of triphenyltetrazolium chloride staining, became evident after 3 h and stabilised at 12 h (42% of left ventricle). The polymorphonuclear leucocyte counts in the hearts, differentiated by staining of their chloroacetate esterase, increased gradually up to 5500 cells per section at 24 h. The leukotriene B4 concentration, determined by radioimmunoassay after freezing of the beating heart in liquid nitrogen, increased to eight times that of the sham operated hearts and peaked at 8 h (9.4(0.6) ng per heart, mean(SEM) n = 5) before the leucocyte counts reached their maximum. A single oral dose of a selective 5-lipoxygenase inhibitor (AA-861, 80 mg.kg-1, 1 h before ligation) lowered the leukotriene B4 concentration to that of the sham operated hearts and decreased the leucocyte count by 49.4% and 41.2% at 12 and 24 h respectively. The inhibitor also reduced the infarct size at 48 h by 34.4%. It was concluded that leukotriene B4, generated in ischaemic cardiac tissue, may increase infarct size through migration of polymorphonuclear leucocytes.

Animals↗
PubMed1988

Possible changes in the leukocyte membrane as a mechanism of leukocyte adhesion to the venular walls induced by leukotriene B4 and fMLP in the microvasculature of the hamster cheek pouch.

Images of the microvasculature of the hamster cheek pouch were projected on TV monitor screen using a monochrome TV camera. Rolling and adhesion of the polymorphonuclear leukocytes on the venular wall were continuously recorded by a newly developed videodensitometer, as changes in average intensity of videosignals in a given detection window superimposed on the screen. Topical application (2.5, 5 and 10 nmol/50 microliter) of fMLP (formyl-methionyl-leucyl-phenylalanine) or superfusion of leukotriene (LT) B4 (0.3, 3 and 30 pmol/ml/min) caused dose-dependent increase in the number of leukocytes adhering to the venules, but a tendency of rolling leukocyte to decrease. Local pretreatment of the microvasculature with a selective 5-lipoxygenase inhibitor (AA-1777) prevented the leukocyte adhesion induced by fMLP (10 nmol/50 microliter), indicating that this adhesion was induced through generation of 5-lipoxygenase products. Selective injection of fMLP (10, 30 and 100 pmol/0.1 microliter) by micropipette into the connective tissue close to the capillary dose-dependently increased the number of leukocytes adhering to the venule downstream, but injection of the highest dose (100 pmol/0.1 microliter) close to the venular wall caused no adhesion to the same venule. Similar results were obtained with LTB4 (30 fmol/0.1 microliter). These findings suggest that fMLP or LTB4 applied topically is absorbed from the capillaries and induces membrane changes in the leukocytes, but not in the endothelial cells, resulting in their adhesion to the venular wall.

Animals↗
PubMed1987

Loss of the activity of human coagulation factor XII by a chymotrypsin-like protease activated in rat mast cells during degranulation with compound 48/80.

Mediator release from mast cells is an initial step in the immediate-type hypersensitivity. Thus, the interaction of neutral proteases released from mast cells with plasma kallikrein-kinin system was investigated. Two proteases, chymotrypsin-like (CHY) and trypsin-like (TRY) proteases, were activated in purified rat mast cells after degranulation with compound 48/80. Three fourths of the CHY activity remained in the cell residue, and the activity was inhibited by chymostatin, whereas most of the TRY activity was released in the medium and was inhibited by leupeptin. The incubation of rat or human plasma with degranulated mast cell (DMC) suspension did not cause the activation of plasma prekallikrein, but did cause a loss in the activity of coagulation factor XII, as ascertained by the lack of activation of prekallikrein in either the DMC-treated plasma by glass powder or in the incubation of DMC-treated human plasma with factor XII deficient plasma activated by kaolin. The prekallikrein and high-molecular-weight kininogen levels were sufficient for activation of factor XII.

Animals↗
PubMed1987

Roles of arachidonate metabolites in thrombus formation and leukocyte migration: analyses at microcirculatory level.

Thromboxane (TX) A2 is involved in platelet aggregation, which initiates thrombus formation. The platelet thrombi in microcirculation, however, are not homogeneous in nature. Two types of platelet thrombi, formed in an arteriole of the hamster cheek pouch, could be differentiated in sensitivity to indomethacin and PGI2. The "stable thrombus" was sensitive to indomethacin, and was not inhibited by PGI2, when applied after the formation, whereas the "ADP-induced thrombus" was sensitive to PGI2, but insensitive to indomethacin. These characteristics were reflected by two types of aggregation of composed platelets. Leukotriene B4 induced adhesion of the leukocytes on the venular wall in very low concentrations, when perfused over the microvasculature of hamster cheek pouch. The leukocyte adhesion on the venular wall was followed by migration into interstitial space. This adhesion was attributed to a change of leukocytes, rather than of the endothelial cell surface, as ascertained by selective microinjection of LTB4 with a glass capillary. LTB4 was also accumulated in the ischemic cardiac tissue after ligation of the rat coronary artery, followed by a peak in the accumulation of leukocytes. Inhibition of the LTB4 generation by a 5-lipoxygenase inhibitor not only suppressed the leukocyte count by 40%, but also the infarct size by 34.4%.

Adenosine Diphosphate↗
PubMed1986

Potentiation of bradykinin-induced nociceptive response by arachidonate metabolites in dogs.

Bradykinin was injected retrogradely into a branch of the splenic artery of lightly anesthetized dogs, and the reflex hypertensive response was used as an indicator of the nociception. The reflex hypertensive response to low doses of bradykinin (less than 1 nmol), but not to high doses (3-5 nmol), was markedly suppressed by infusion of indomethacin (0.54 mumol/min) into the splenic artery. During indomethacin infusion, the reflex hypertensive response to low doses of bradykinin was potentiated dose dependently by the following arachidonic acid metabolites (ED50): prostaglandin (PG)I2 (2.9 nmol) greater than or equal to PGH2 (4.4) greater than PGE2 (14) = thromboxane (TX)A2(15) greater than PGD2 (greater than 100). Leukotrienes B4, C4 and D4 showed practically no activity. This potentiating effect lasted up to 20 min after injection, particularly with PGE2. These results may not exclude the role of PGI2 as a major candidate for involvement in bradykinin-induced nociception, although a selective TX synthetase inhibitor (OKY-046) showed a weak analgesic effect (only 1/30 that of indomethacin).

Animals↗
PubMed1986

Independent consumption of high and low molecular weight kininogens in vivo.

The levels of high molecular weight (HMW) kininogen and pre-kallikrein in rat plasma were markedly reduced after single injection of bromelain (10 mg/kg, i.v.) and gradually recovered over a 72 hour period. The level of low molecular weight (LMW) kininogen, however, was not changed during this period. Rat pleurisy was induced by intrapleural injection of lambda-carrageenin. The levels of HMW kininogen and prekallikrein, but not of LMW kininogen, in the exudate were markedly decreased, when compared with those in plasma of the same animals. After pretreatment with disulfiram, oral administration of ethanol (2 g/kg) or intravenous injection of acetaldehyde (10 mg/kg) to rats caused significant decrease in the plasma level of LMW kininogen with no significant effect on the plasma HMW kininogen and prekallikrein levels. These results suggest that HMW and LMW kininogens may be consumed separately in vivo and play different roles.

Animals↗
PubMed1986

Different modes of interaction of bradykinin with prostaglandins in pain and acute inflammation.

A mode of interaction of bradykinin with prostaglandins (PGs) in pain were compared with that in acute inflammation. When pain production was measured as an increase in reflex hypertensive response of the lightly anesthetized dogs after intrasplenic injection of bradykinin, the response was dependent to the doses (0.3-5 nmol) of bradykinin and that by the small doses (0.1-1 nmol) was blocked by intrasplenic infusion of indomethacin (0.54 mumol/min). The response to the threshold dose of bradykinin (0.3 nmol), which was suppressed during the indomethacin infusion, was potentiated by simultaneous injection of exogenous PGs. Order of the potency was PGI2 greater than PGH2 greater than PGE2 = TXA2 much greater than PGD2. Thus, it is clear that bradykinin induced pain through the generation of one of prostaglandins. On the other hand, the activity of bradykinin in plasma leakage was potentiated by simultaneous injection of PGE2, when tested in rabbit skin. In rat carrageenin-induced pleurisy, plasma prekallikrein was activated and high molecular weight (HMW) kininogen, not low molecular weight (LMW) kininogen, was consumed in the pleural cavity in the entire course of the pleurisy. Bradykinin played a role in plasma exudation in the pleurisy, because the plasma leakage was markedly inhibited in the rats, in which prekallikrein and HMW kininogen in plasma were depleted by intravenous bromelain. PGE2 was found in the pleural exudate, but the contribution of PGE2 itself to the plasma exudation seems to be only 10%. On the basis of the bradykinin release in the pleural cavity, once the PGE2 release was superimposed, the maximal plasma leakage was observed, indicating that PGE2 was released independently from bradykinin, and potentiated the plasma leakage by bradykinin.

Animals↗
PubMed1986

Release of endogenous prostaglandins by mild hyperosmotic saline inhibits tetragastrin-stimulated gastric acid secretion in rats.

Filling of the gastric lumen of rats with 1.0 M NaCl solution (5 ml) for 10 min under urethane anesthesia caused an increase in the gastric fluid concentrations of prostaglandin (PG) E2, 13,14-dihydro-15-keto-PGE2 and 6-keto-PGF1 alpha as determined by radioimmunoassay. PGE2 was the major PG generated. The levels of PGE2 in the gastric fluid were increased dose-dependently after filling the lumen with 0.3, 0.5, 0.7 or 1.0 M NaCl solutions. The pH of the gastric fluid increased similarly after 0.5 to 1.0 M NaCl solutions. Indomethacin (10 mg/kg, i.p.) suppressed the PGE2 increase caused by 1.0 M NaCl solution, but did not prevent the increase of the pH of the gastric fluid induced by intragastric 1.0 M NaCl. Infusion of tetragastrin (62.5 micrograms/kg/hr, i.v., for 10 min) caused a marked increase of acid secretion without modifying intragastric concentration of PGE2. The acid secretion due to tetragastrin was completely inhibited after intragastric administration of 1.0 M NaCl solution, while indomethacin restored the tetragastrin-induced acid secretion, with prevention of a rise of intragastric PGE2 levels. These observations suggest that 1.0 M NaCl solutions suppress basal intragastric acid through a mechanism which is independent of prostaglandins. In contrast, the suppression of tetragastrin-induced acid secretion by intragastric 1.0 M NaCl solution appears to be mediated through a release of prostaglandins.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Difference in the in vitro metabolism of leukotrienes in the exudates from allergic and nonallergic rat pleurisies.

The metabolism of leukotrienes (LTs) in the cell-containing inflammatory exudate of rat pleurisy was studied in vitro. The exudates of both nonallergic carrageenin-induced pleurisy and IgG immune complex-mediated pleurisy converted 3H-LTB4 to 20-OH LTB4, but virtually did not metabolized 3H-LTC4 or 3H-LTE4 up to 2 hrs. 3H-LTD4 was changed to LTC4 by the exudate of non-allergic pleurisy, whereas 3H-LTD4 was metabolized to LTE4 by that of allergic pleurisy. Reflecting on the different metabolism, the gamma-glutamyl transpeptidase activity in the exudate of carrageenin-induced pleurisy was significantly higher than that in IgG immune complex mediated pleurisy. The enzyme activity was not derived from the blood itself, but from the infiltrated polymorphonuclear leukocytes. The activity of the cell homogenate in both exudates was not significantly different. Thus, it could be concluded that the difference in the metabolism of LTD4 between the nonallergic and allergic pleural exudates in vitro was mainly attributable to the enhanced activity of the gamma-glutamyl transpeptidase released in the exudate.

Animals↗