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Biomedical subjects

K Tsurumi

Publications and source records attributed to K Tsurumi.

At least 37 records · Page 2Linked to original sources
PubMed1989

Pathological studies on nephrotoxic serum nephritis accelerated with rabbit gamma-globulin in mice.

In order to characterize nephrotoxic serum nephritis accelerated with rabbit gamma-globulin in mice, histopathological studies were carried out 15 days after NTS injection, the time when increases in urinary protein and serum cholesterol and a decrease in serum albumin were apparent. Characteristic changes were widespread thickening of glomerular capillary walls and widening of mesangial areas, owing to deposits of mesangial matrixlike substances. The mesangial interposition into subendothelial areas and the resultant narrowing of the capillary lumen were shown ultrastructurally. In severely affected glomeruli, a hyaline nodular lesion was observed. Visceral epithelial cells demonstrated fusion of the foot processes, microvilli formation, occasional proliferation, and enlargement. Parietal epithelial cells proliferated, forming a cellular crescent. Based on these characteristics, it appears this nephritic model shares a common pathology with human membranoproliferative glomerulonephritis type 1 and crescentic glomerulonephritis and can be considered an appropriate model for producing severe nephritis for short periods.

Animals↗
PubMed1989

Platelet prostaglandin E1 hyposensitivity in schizophrenia: reduction of prostaglandin E1- or forskolin-stimulated cyclic AMP response in platelets.

Cyclic 3',5'-adenosine monophosphate (cAMP) formation via prostaglandin E1 (PGE1)-or forskolin-stimulation were determined in washed intact platelets from 32 schizophrenic patients and 30 normal controls. Regarding basal cAMP levels in the platelets, there were no differences between schizophrenic patients and normal controls. Both PGE1-and forskolin-stimulated cAMP response reduced in platelets from schizophrenics compared with normal controls. These results suggested that platelets in schizophrenics were impaired not only in the adenylate cyclase unit per se but also extensively in the cAMP generating system coupled to a PGE1 receptor.

Adenylyl Cyclases↗
PubMed1989

[Kappa-type opioid receptor in human placental membrane].

Since many opioid receptor preparations are heterogeneous systems containing multiple types of receptor, characterization of each type of the receptor is influenced by contamination with other types of receptor. Demonstrating kappa receptor proved more difficult owing to the ability of kappa ligands to interact with a number of receptor classes and to the lack of the homogeneous preparation. It has been reported that kappa ligands selectively bind to human placental membrane. To establish homogeneous kappa receptor preparation, the kappa binding to human placenta was characterized. The portion which was predominantly villus tissue was removed from freshly collected placenta, and the P3-membrane fraction was prepared. Kappa opioid agonist, such as 3H-Dynorphin A, 3H-ethylketocyclazocine and 3H-U-69593, bound to the human placental membrane fraction in a manner of single class of binding site (Bmax: approximately 40 fmol.mg-1 protein). In contrast, 3H-dihydromorphine, 3H-DAGO (mu agonist), 3H-DADLE (delta agonist) or 3H-SKF-10047 (sigma agonist) showed no binding activity. The specific binding of 3H-diprenorphine was displaced only by kappa-selective ligand (U-50488H, dynorphin, butorphanol). These results suggest that opioid binding in human placental membrane is specific for kappa opioid.

Humans↗
PubMed1987

[Characterization of adrenal medullary opioid receptors. I. Binding of opioids to adrenal medullary opioid receptors].

We studied the binding of [3H]D-Ala2-D-Leu5-enkephalin ([3H]DADLE) and [3H] diprenorphine to crude plasma membrane fraction obtained from the bovine adrenal medulla (bovine adrenal medullary membranes) in order to characterize adrenal medullary opioid receptors. The [3H] diprenorphine binding was the highest in crude plasma membrane-mitochondrial fraction among all subcellular fractions studied. The amount of [3H] diprenorphine bound to bovine adrenal medullary membranes was proportional to the protein concentration. Association kinetics of the [3H] diprenorphine binding to bovine adrenal medullary membranes showed that the maximal binding was achieved following 8 min incubation and that the binding conformed the second-order kinetics. [3H] DADLE and [3H] diprenorphine bound to bovine adrenal medullary membranes with high affinities. The Kd and Bmax for the [3H] DADLE binding were found to be 2.9 nM and 57.5 fmole/mg protein, respectively, while those for the [3H] diprenorphine binding were 0.31 nM and 250 fmole/mg protein, respectively. Displacement studies showed that the [3H] diprenorphine binding was inhibited dose-dependently by levorphanol, dynorphin (1-13), beta-endorphin and DADLE. Levorphanol was at least 1000-fold more potent to inhibit the [3H] diprenorphine binding than dextrorphan, indicating stereospecificity of the [3H] diprenorphine binding. Na+, Li+ and K+ (100 mM) diminished the [3H] DADLE binding and enhanced [3H] diprenorphine binding. Na+ (100 mM) increased the Kd value for the [3H] DADLE binding from 2.9 nM to 14.1 nM. Mn++, Ca++ and Mg++ diminished the [3H] diprenorphine binding. Mn++ (1 mM) increased the Bmax value for the [3H] DADLE binding from 95 fmole/mg protein to 450 fmole/mg protein. These effects of Na+ and Mn++ on the [3H] diprenorphine binding were found to be dose-dependent. [3H] Diprenorphine binding to the digitonin-solubilized opioid receptor was also inhibited dose-dependently by Mn++. These results suggest that bovine adrenal medullary membranes contain high affinity and stereospecific opioid receptors and that the binding of opioids to the bovine adrenal medullary opioid receptors is influenced by cations. Binding study also revealed the presence of opioid receptors in human malignant pheochromocytoma. The Kd and Bmax of the [3H] diprenorphine binding to crude membrane fraction obtained from malignant pheochromocytoma were found to be 0.14 nM and 10.4 fmole/mg protein, respectively.

Adrenal Medulla↗
PubMed1987

[Characterization of adrenal medullary opioid receptors. II. Coupling of adrenal medullary opioid receptors to GTP binding proteins].

We studied possible coupling of opioid receptors to GTP-binding proteins to clarify the mechanism(s) of opioid action in bovine adrenal medullary membranes. Guanylyl imidodiphosphate (Gpp(NH)p) reduced the binding of [3H] D-Ala2-D-Leu5-enkephalin ([3H] DADLE) to bovine adrenal medullary membranes dose-dependently, and enhanced the binding of [3H] diprenorphine to them. Gpp(NH)p (0.1 mM) enhanced the Kd value of the [3H] DADLE binding from 2.9 nM to 3.9 nM, but did not change its Bmax. Pretreatment of bovine adrenal medullary membranes with pertussis toxin (PT) reduced the [3H] DADLE binding. The Gpp(NH)p inhibition for [3H] DADLE binding was diminished by the PT-pretreatment. On the other hand, the [3H] diprenorphine binding to PT-pretreated membranes was higher than that to control membranes. Levorphanol inhibited the adenylate cyclase activity of the rat caudate nucleus crude synaptosomal fraction, but did not change that of bovine adrenal medullary membranes. These results suggest that opioid receptors in bovine adrenal medullary membranes are coupled to PT-sensitive GTP-binding protein which may not influence on adenylate cyclase.

Adenylate Cyclase Toxin↗
PubMed1987

Coupling of adrenal medullary opioid receptors to islet-activating protein-sensitive GTP-binding proteins.

Possible coupling of bovine adrenal medullary opioid receptors to islet-activating protein (IAP, pertussis toxin)-sensitive GTP-binding proteins was investigated by studying effects of guanyl-5'-yl imidodiphosphate (Gpp(NH)p) and IAP treatment of membranes on opioid binding. Gpp(NH)p inhibited [3H]D-Ala2-D-Leu5-enkephalin ([3H]DADLE) binding by increasing the dissociation constant of [3H]DADLE and membranes, and enhanced slightly [3H]diprenorphine binding. IAP treatment of membranes reduced [3H]DADLE binding and abolished almost completely the Gpp(NH)p inhibition of [3H]DADLE binding. Treatment of membranes with IAP and [32P]NAD resulted in radio-labeling of membrane proteins of approximately 39,000 dalton. DADLE inhibited adenylate cyclase activity in rat brain caudate nucleus. However, DADLE, beta-endorphin, levorphanol and dynorphin A(1-13) did not show any significant inhibitory action on bovine adrenal medullary adenylate cyclase activity. These results suggest that bovine adrenal medullary opioid (DADLE) receptors are linked to IAP-sensitive GTP-binding proteins which are not directly coupled to adenylate cyclase.

Adenylate Cyclase Toxin↗
PubMed1986

Opioid and non-opioid binding of beta-endorphin to bovine adrenal medullary membranes.

Binding of human beta-endorphin (beta h-EP) to bovine adrenal medullary membranes was characterized using [125I]Tyr27-beta h-EP [( 125I]beta h-EP) as a primary ligand. The specific binding of [125I]beta h-EP was time-dependent, saturable and stereospecific. Analysis of a saturation isotherm revealed two apparent classes of specific binding sites with dissociation constants of 2.4 and 34 nM. The extent of maximum inhibition of specific [125I]beta h-EP binding by either levorphanol, morphine, naloxone, dynorphin A (1-13) or D-Ala2-D-Leu5-enkephalin was similar to each other and remained partial (60-70%). Levorphanol eliminated the high affinity component but showed no effect on the low affinity component of [125I]beta h-EP binding. beta h-EP(1-31) displaced completely the [125I]beta h-EP binding. However, beta h-EP(1-23) only partially (approximately 80%) inhibited the [125I]beta h-EP binding. beta h-EP(6-31) showed inhibitory activity on [125I]beta h-EP binding. These results suggest that [125I]beta h-EP binding to bovine adrenal medullary membranes consists of a high affinity opioid-sensitive component and a low affinity non-opioid component. The non-opioid component of [125I]beta h-EP binding may be related to COOH-terminal of the beta h-EP molecule.

Adrenal Medulla↗
PubMed1986

Adrenal medullary opioid receptors are linked to GTP-binding proteins, pertussis toxin substrates.

Effects of Gpp(NH)p and pretreatment of membranes with pertussis toxin (PT) were studied on opioid binding to bovine adrenal medullary opioid receptors. Gpp(NH)p inhibited [3H]DADLE binding by increasing the dissociation constant. PT treatment reduced [3H]DADLE binding and almost abolished the Gpp(NH)p inhibition of [3H]DADLE binding. Levorphanol did not show any significant effect on bovine adrenal medullary adenylate cyclase activity. These results suggest that bovine adrenal medullary opioid receptors are linked to PT-sensitive GTP-binding proteins which are not directly coupled to adenylate cyclase.

Adenylate Cyclase Toxin↗
PubMed1986

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 2nd communication: inhibitory effects on acute inflammation and prostaglandin-related reactions.

Since a newly synthesized nonsteroidal antiinflammatory drug (NSAID) having weaker effects on gastrointestinal tract, 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid (CN-100), was found to markedly inhibit rat paw edema induced by carrageenin and other phlogists, the effects of the drug on other acute inflammatory reactions and prostaglandins (PGs)-related reactions were compared with those of known NSAID in this study. At even a large dose of CN-100, 20 mg/kg, the drug did not significantly inhibit the increased vascular permeability induced by histamine in rat skin, but CN-100 could dose-dependently inhibit the increased vascular permeability induced by acetic acid in mouse peritoneum. The inhibitory activity of CN-100 in the latter was equivalent to that of pranoprofen and indometacin. CN-100 exerted a potent inhibitory action on erythema induced by UV irradiation, which was equal to and 3 times stronger than pranoprofen and indometacin in activity, respectively. Since PGs participate in these acute inflammatory reactions, the effects of CN-100 on reactions relevant to PGs were examined. The drug at dose levels lower than antiinflammatory doses could prevent acute death and diarrhea induced by i.v. injection of arachidonic acid in rabbits and endotoxin in mice, respectively, suggesting that the drug had a potent inhibitory action on biosynthesis of PGs. The adverse effects of CN-100 on gastric and small intestinal mucosa was very weak, the activity being about one-tenth of that of pranoprofen and indometacin.

Animals↗
PubMed1986

Effect of the new antiallergic drug 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid on inflammatory reactions and platelet aggregation.

A new chemical compound, 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid (Sm 857), known to have antiallergic activity was investigated with respect to its antiinflammatory effect. Sm 857 did not inhibit ultraviolet-induced erythema in guinea pigs, intradermal increased vascular permeability induced by histamine in rats and carrageenin-induced edema of the rat hind paw. Further, the compound showed no influence on wound healing in rats and was observed to exert neither analgesic nor inhibitory effect on platelet aggregation. Sm 857 was thus found to have no effect at all on acute and chronic inflammatory reactions. It was denied, therefore, that any antiinflammatory effect might be involved in the antiallergic effect of Sm 857 but it may be related to an inhibitory effect on the release of mediators or on some earlier stage. Therefore investigation was carried out into its inhibitory action on dextran- and compound 48/80-induced edema of the rat hind paw. As a result, Sm 857 showed a stronger inhibitory effect on dextran edema than tranilast. Sm 857 inhibited endotoxin-induced diarrhea in mice and the effect was similar to that of tranilast, suggesting its inhibitory action on the release of mediators.

Animals↗
PubMed1986

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 1st communication: inhibitory effects of rat paw edema.

In the development process of a new nonsteroidal antiinflammatory drug (NSAID) with less toxicity and side-effects, 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepein-2-yl) propionic acid (CN-100) was chosen as the most excellent NSAID from synthetic tricyclic compounds after screening test. For the series of studies on antiinflammatory effects of this compound in detail, its effect on rat paw edema induced by various phlogists was first investigated. The inhibitory effect of CN-100 on carrageenin-induced edema was remarkable and nearly equal to that of indometacin. The effect was not affected by continuous administration for 2 weeks or adrenalectomy. Similarly to indometacin, CN-100 had no significant effect on yeast-induced edema mediated by 5-hydroxytryptamine and concanavalin-A-induced edema unrelated with prostaglandins. However, CN-100 displayed a weaker inhibitory effect on nystatin-induced edema than indometacin, suggesting that CN-100 has a low membrane stabilizing action and a strong blocking action on synthesis of prostaglandins. CN-100 inhibited the sustained edema induced by mustard, but the drug did not interfere with the increase in body weight of rats. Indometacin in the same dose caused decrease in body weight and death. The toxicity of CN-100 was definitely less than that of indometacin, although both drugs were similar in antiinflammatory activity and mode of action on rat paw edema. Results suggest that CN-100 is an effective drug on not only acute but also subacute and chronic inflammation.

Adrenalectomy↗
PubMed1986

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 3rd communication: inhibitory effects on leucocyte emigration and proliferation of granulation.

The effects of 2-(10,11-dihydro-10-oxodibenzo [b,f]thiepin-2-yl)propionic acid (CN-100), which has a significant inhibitory effect on acute inflammatory reactions, on leucocyte emigration and proliferation of granulation were examined in this study. The compound obviously inhibited the protein exudation and polymorph emigration 6 h after application of carboxymethylcellulose pouch method. It also definitely inhibited the monocyte emigration occurring 24 h after carrageenin pleurisy, and the inhibitory activity of the compound was nearly equal to that of pranoprofen and weaker than that of indometacin. CN-100 inhibited the proliferation of granulation in the test by paper disk method, i.e., the compound inhibited wound healing. The antigranulation activity of CN-100 was also nearly equal to that of pranoprofen and weaker than that of indometacin. These results proved that CN-100 should definitely inhibit the reactions of the second and third inflammatory phases of the whole reactions from the exudative phase throughout proliferative phase, suggesting that the compound is a useful antiinflammatory drug.

Animals↗
PubMed1986

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl]propionic acid. 4th communication: inhibitory effects on rat adjuvant arthritis.

The preventive and therapeutic effects of 2-(10,11-dihydro-10-oxodibenzo [b,f]thiepin-2-yl)propionic acid (CN-100) on local and systemic changes of rats with adjuvant arthritis being used frequently as experimental model of rheumatoid arthritis were investigated in comparison with those of reference drugs, indometacin and pranoprofen. Preventively and therapeutically CN-100 showed potent inhibitory effects on adjuvant primary inflammation and secondary lesion. CN-100 also exerted an evident preventive effect on destruction of foot bone, improved the changes in organ weight, and stimulated weight gain. These effects were dose-dependent, and the effects at 5.0 mg/kg were almost the same as those of indometacin and pranoprofen at 1.25 and 2.5 mg/kg, respectively. The mode of action of CN-100 resembled that of reference compounds. Although CN-100 improved the change in albumin/globulin ratio, which was a parameter of systemic inflammatory reactions, the effect was more remarkable in therapeutic administration than in preventive one. This suggests that CN-100 is suitable for clinical application.

Animals↗
PubMed1986

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 5th communication: antiplatelet effect of the drug and antiinflammatory effect of its main metabolite.

Since nonsteroidal antiinflammatory drugs (NSAID) usually have an antiplatelet effect, the inhibitory effect of 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl) propionic acid (CN-100), which exerts a potent antiinflammatory effect, was compared with those of reference drugs, indometacin and pranoprofen, in this study. Indometacin at 10(-5) mol/l inhibited completely (100%) rat and rabbit platelet aggregation induced by collagen and arachidonic acid. Pranoprofen at 10(-5) mol/l also entirely inhibited rat platelet aggregation induced by the two aggregators, but an about 10 times higher concentration was required to produce 100% inhibition of rabbit platelet aggregation. CN-100 at 10(-5) mol/l exerted 100% inhibition of rat platelet aggregation induced by collagen, whereas more than 10(-4) mol/l was needed to exhibit 100% inhibition of aggregation induced by arachidonic acid and ADP. The inhibitory activity of CN-100 on aggregation of rat platelets ex vivo was weaker than those of reference NSAID, i.e., the antiplatelet effect of CN-100 was found to be weak. The main metabolite of CN-100 also had a weak antiplatelet effect, and its antiinflammatory effect on carrageenin edema and UV erythema was apparently weaker than that of CN-100. The inhibitory effect of the metabolite on endotoxin diarrhea was weak. The ulcerogenic effect of the metabolite on gastric mucosa was similar to that of CN-100, but the effect rarely seemed to be a clinical problem because it was basically weak.

Animals↗