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Biomedical subjects

N Nakata

Publications and source records attributed to N Nakata.

69 records · Page 4Linked to original sources

Physical dependence of a dermorphin tetrapeptide analog, [D-Arg2, Sar4]-dermorphin (1-4) in the rat.

The characteristics of an analog of tetrapeptide dermorphin (H-Tyr-D-Arg-Phe-Sar-OH), [D-Arg2, Sar4]-dermorphin (1-4) were examined in comparison with morphine by the appearance of typical withdrawal signs upon cessation of administration or treatment with naloxone, an opioid antagonist. The dose of [D-Arg2, Sar4]-dermorphin (1-4) or morphine in the physical dependence test can be quantified by determining the ED50 to inhibit the tail-flick response to thermal stimuli. Doses from 8 to 64 times the ED50 doses were employed in the subcutaneous injection schedules. The cessation of [D-Arg2, Sar4]-dermorphin (1-4) or naloxone treatment was largely without effect on body weight, in contrast to a marked loss of weight in morphine-dependent rats. The tetrapeptide failed to substitute for morphine in morphine-dependent rats. The physical dependence of [D-Arg2, Sar4]-dermorphin (1-4) was revealed by the behavioral signs of withdrawal precipitated by naloxone. However, the scores of lacrimation, diarrhea and urination were much lower in chronically tetrapeptide-treated rats than in morphine-treated rats, though the score of teeth chatter was higher. These findings indicate that [D-Arg2, Sar4]-dermorphin (1-4) may differ from morphine in physical dependence.

Analgesics↗

Comparison of the antinociceptive effect between D-Arg containing dipeptides and tetrapeptides in mice.

D-Arg containing dipeptides, H-Tyr-D-Arg-OMe and H-Tyr (Et)-D-Arg-OMe, and D-Arg2 substituted N-terminal tetrapeptides of dermorphin, H-Tyr-D-Arg-Phe-Gly-OEt and H-Tyr (Et)-D-Arg-Phe-Gly-OEt administered intracerebroventricularly exhibited dose-dependent antinociceptive activities in mice as measured by the tail pressure and phenylbenzoquinone writhing tests. The effects of these peptides used were significantly antagonized by the pretreatment with naloxone, indicating that these effects must be produced through opioid receptors. Furthermore, it is of conspicuous interest that the effects of tetrapeptides revealed in infinitestimal order (ED50 = 12.5 and 355.0 pmole in the tail pressure test and 3.1 and 53.0 pmole in the phenylbenzoquinone writhing test, respectively) and was much more potent and prolonged than those of morphine, not to mention dipeptides used. However, judging from the difference of peak times and the degree of the antagonism by naloxone, it was suggested that dipeptides and tetrapeptides used might act on different sites of action in the central nervous system.

Analgesia↗

Experimental myositis ossificans: cartilage and bone formation in muscle in response to a diffusible bone matrix-derived morphogen.

Bone matrix gelatin, prepared by chemical extraction of soluble noncollagenous proteins, was half digested with a chromatographically purified collagenase. The residue was placed on one side and autologous muscle on the other side of cellulose acetate membranes in diffusion chambers and tissue cultures. In this avascular system, the muscle septa connective tissue proliferated and differentiated into cartilage. Muscle tissue cultured in media conditioned with matrix residues and then transferred into a vascularized muscle pouch differentiated into cartilage and bone. These observations form the basis for a working hypothesis that myositis ossificans is a response of new populations of proliferating intramuscular connective tissue cells to a bone matrix-derived diffusible molecule.

Animals↗

Uptake of uric acid by separated renal tubules of the rabbit. I. Characteristics of transport.

A rapid filtration procedure was used to determine rates of uric acid uptake by a preparation of separated renal cortical tubules of the rabbit. The rate of uric acid uptake was temperature dependent and showed saturation kinetics with a K of 3.2 mM. The uptake was 50% lower when measured under nitrogen as compared with uptake under oxygen. The uptake rate increased with increasing sodium concentration and decreased with increasing potassium concentration. Uptake was stimulated by citrate, succinate and pyruvate, and inhibited by alpha-ketoglutarate. Parathyroid hormone and 10(-4) M adenosine 3':5'-monophosphate increased the uric acid uptake rate when preincubated with the tubules for 130 minutes before the addition of uric acid. Uric acid uptake in this preparation appears to occur by some form of carrier-mediated active transport.

Animals↗

An osteosarcoma cell and matrix retained morphogen for normal bone formation.

Histophysiology, ultrastructure, chemical analyses of transplants and implants of Dunn and Ridgway mouse osteosarcomas demonstrate that tumorigenesis is a manifestation of deranged morphogenesis in developing mesenchymal cell populations. The end product of development is defective, incompletely calcified, disorganized bone without any inclusions of bone marrow tissue. When Dunn osteosarcoma is freeze-dried and then implanted, the tumor is resorbed and replaced by deposits of normal cartilage, bone, and bone marrow. Freeze-dried Ridgway osteosarcoma is replaced only by a fibrous connective tissue scar. Disaggregated Dunn tumor osteoblasts synthesize a trypsin-labile collagenase-resistant cell surface localized bone morphogen. Tumor matrix stroma, prepared by sequential chemical extraction of soluble non-collagenous proteins also contains significant quantities of the same bone morphogen. Tumor tissue pulverized to particle size as small as 44 micrometer3 transmitted bone morphogen more rapidly than intact tumor tissue. The total tumor cell and stroma mediated bone morphogen produces three times more normal bone than normal cortical bone matrix. Our working hypothesis is that a normal bone morphogenetic polypeptide (BMP) is synthesized by Dunn osteosarcoma cells and retained by the tumor matrix stroma. Neither the mechanism of transmission nor the mesenchymal cell receptor sites of BMP are known.

Alkaline Phosphatase↗

Uptake of uric acid by separated renal tubules of the rabbit. II. Effects of drugs.

The effect of various drugs on the rate of uptake of uric acid by separated renal tubules of the rabbit was investigated. Determinations were made of 150 values and slopes of the inhibition curves. The most potent inhibitor of uric acid uptake was sulfinpyrazone, with an 150 of 0.02 mM. Calcium ipodate and benzbromarone were also potent inhibitors. Uricosuric drugs, with the exception of benzbromarone, had shallow inhibition slopes. Diuretic drugs had steep inhibition slopes. More than one mechanism of action is probably involved in the inhibition of uric acid uptake in separated renal tubules by drugs.

Animals↗

Enhanced firefly bioluminescent assay of adenosine 5'-triphosphate using liposomes containing cationic cholesterols.

Cationic liposomes composed of phosphatidylcholine and cationic cholesterols were prepared by extrusion technique. Dimethylaminoethyl-carbamoyl cholesterol (DMAE-chol) and diethylaminoethyl-carbamoyl cholesterol (DEAE-chol) were synthesized as a cationic cholesterol. Cationic liposomes containing DMAE-chol and DEAE-chol enhanced the intensity of maximum light emission from the firefly bioluminescent (BL) reaction. The sensitivity for ATP in the presence of cationic liposomes containing DMAE-chol and DEAE-chol was improved by a factor of 10 times compared to that in water alone. The detection limit for ATP upon using cationic liposomes was 1.0 pmol/L in an aqueous standard solution. The BL enhancement in the presence of cationic liposomes could be explained in terms of BL emitters and electrostatic interaction between the liposomes surface and BL reactants.

Adenosine Triphosphate↗

Antinociceptive cross-tolerance between [D-Arg2]-dermorphin tetrapeptide analogs and morphine.

Cross-tolerance between [D-Arg2]-dermorphin tetrapeptide analogs and morphine with respect to antinociception was examined in the present set of experiments. Systemic administration of H-Tyr-D-Arg-Phe-Gly-NH2 (TDAPG-NH2), H-Tyr-D-Arg-Phe-beta-Ala-OH (TDAPA) or morphine over a period of 5 days produced the development of tolerance. In the cross-tolerance study, antinociception after subcutaneous (SC), intracerebroventricular (ICV) and intrathecal (IT) administrations of TDAPG-NH2 and TDAPA in morphine-tolerant mice was not significantly different from their respective effects in saline-pretreated control mice. A marked tolerance to SC- and ICV-administered morphine was seen in mice made tolerant to TDAPG-NH2 and TDAPA. However, IT administration of morphine produced no significant decrement in the antinociceptive activity in mice made tolerant to TDAPG-NH2 and TDAPA. These data indicate that [D-Arg2]-dermorphin tetrapeptide analogs can produce significant antinociception in morphine-tolerant mice.

Amino Acid Sequence↗

Mycobacterium leprae DNA in daily using water as a possible source of leprosy infection.

Some environmental factors were suspected to be sources of leprosy infection according to the results of total survey in the highly endemic villages in Indonesia. M. leprae DNA were detected by PCR from 21 out of 44 water sources used daily by villagers. Prevalence of leprosy among the people using PCR-positive water for bathing and washing was significantly higher than that among the people who used PCR-negative water. No significant difference in prevalence was, however, recognized in case of usage of negative or positive water for drinking. Water was regarded as a reservoir and infectious source of M. leprae. Transmission of leprosy through the contaminated water was strongly suggested by epidemiological analysis.

DNA, Bacterial↗

Protective effects of a novel calcium antagonist with platelet-activating factor-antagonistic action, F-0401, against ischemic brain damage.

The protective effects of a novel dihydropyridine calcium antagonist with platelet-activating factor-antagonistic action, F-0401, on ischemic brain damage were investigated using experimental ischemia models in rats and gerbils. F-0401 (1 and 10 mg/kg, i.p.) prevented increases in water content, determined by the wet-dry method, in ischemic areas 24 hr after 1 hr of middle cerebral artery occlusion in the rat. Pretreatment with F-0401 (1 and 10 mg/kg, i.p.) prevented extravasation of Evans blue dye in the brain following 2 hr of bilateral carotid artery occlusion and 2 hr of reperfusion in the rat. Pretreatment with F-0401 (1 and 10 mg/kg, i.p.) protected against neuronal damage to hippocampal CA1 pyramidal cells following 3 and 5 min of forebrain ischemia in the gerbil. Immunostaining against microtubule-associated protein-2 also demonstrated preservation of CA1 neurons in F-0401-treated animals. Thus, this study shows that F-0401 prevents the occurrence of brain edema, disruption of blood-brain barrier and neuronal damage caused by cerebral ischemia. The results demonstrate that F-0401 may be a powerful candidate as a therapeutic agent in the treatment of acute stroke in man.

Animals↗