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K Furuno

Publications and source records attributed to K Furuno.

At least 109 records · Page 6Linked to original sources
PubMed1990

Immunocytochemical study of the surrounding envelope of autophagic vacuoles in cultured rat hepatocytes.

By the use of electron immunoperoxidase cytochemistry at the ultrastructural level, the relationship of the surrounding sac of the autophagic vacuoles to the different cytomembranes was studied. When the endoplasmic reticulum was completely stained for microsomal carboxyesterase E1, the enzyme was not found to be labeled in the developed envelopes forming autophagic vacuoles. The autophagic envelope at the formative stages was also devoid of albumin which intensely stained Golgi cisternae. However, although it was rare, the endoplasmic reticulum showed an electron-lucent region like an early autophagic envelope in its cisternae which was lacking in carboxyesterase E1. In addition, deeply curving swelled cisternae where carboxyesterase E1 was found at the edges were occasionally encountered. These observations suggest that the segregating membranes arise from an endoplasmic reticulum and the structural characteristics of the endoplasmic membranes change at very early stages of formation of autophagic vacuoles. Acid phosphatase, a lysosomal marker enzyme, began to be localized on sections of the double membranes of newly created autophagic vacuoles. The enzyme spread all along the limiting membranes of the autophagic vacuoles, while, at the same time, the double membranes were converted into a single membrane. A lysosomal membrane glycoprotein (LGP107) was also localized on the surrounding envelope of autophagic vacuoles in a fashion similar to that of acid phosphatase. Lysosomal hydrolases seem to play some role in the conversion of double limiting membranes into a single limiting membrane.

Acid Phosphatase↗
PubMed1990

Effects of standard cigarette and nicotine-less cigarette smoke inhalings on nicorandil plasma levels in rats.

The influence of cigarette smoke on nicorandil plasma levels at a dose of 10 mg/kg administered orally was investigated in rats. The animals were exposed to standard and nicotine-less cigarette smoke for 8 min using a 'smoking machine'. In nonsmoking control rats, nicorandil plasma levels increased rapidly and reached the maximum (approx. 7.6 micrograms/ml) after 1 h and then decreased gradually. On the other hand, nicorandil plasma levels in the rats inhaling standard cigarette and nicotine-less cigarette smoke reached the maximum (approx. 4.7 and 4.9 micrograms/ml, respectively) after 1-2 h. These results suggest that nicorandil plasma levels after oral administration are influenced not only by standard cigarette smoke but also by nicotine-less cigarette smoke.

Administration, Oral↗
PubMed1990

Purification and characterization of a major glycoprotein in rat liver lysosomal membrane.

A major lysosomal membrane glycoprotein (LGP107) which has an apparent molecular weight (Mr) of 107 kilodaltons (kDa) was purified from rat liver by a simple method with a yield of 1 mg/87 g wet weight of liver. The purification procedures include; preparation of tritosomal membranes of triton-filled lysosomes (tritosomes), extraction of tritosomal membranes by Lubrol PX, wheat germ agglutinin (WGA)-Sepharose affinity chromatography, and monoclonal antibody-Sepharose affinity chromatography. The quantitative immunoblot analysis indicated that LGP107 represents 6.2% of the total protein of tritosomal membranes. The isoelectric point of the purified glycoprotein was 2.7, and it moved toward neutral pH after sialidase treatment, with its molecular weight decreased by about 10 kDa. LGP107 contained 52% carbohydrates, and the carbohydrate moiety was compared of Fuc, Man, Gal, GlcNAc and sialic acid in a molar ratio of 7.2:68.2:40.6:63.0:32.3, respectively, indicating that LGP107 was highly glycosylated with N-linked complex-type olgosaccharide chains. Out of the N-linked glycans released from the glycoprotein by hydrazinolysis/N-reacetylation, about 70% was sialylated. Anion exchange and reverse-phase high performance liquid chromatography analysis on the structure of N-glycans revealed that a disialyl biantennary form is a major component in the oligosaccharide chains of LGP107.

Animals↗
PubMed1990

Behavioral effects of HR-592, a new derivative of indole.

Effects of HR-592 on various behaviors were investigated in rats and mice. 1) HR-592 at doses of 10-100 mg/kg, p.o., and chlorpromazine at doses of 2.5-20 mg/kg, p.o., suppressed dose-dependently spontaneous activities of mice. 2) In the mice treated with HR-592, 10 and 30 mg/kg, p.o., and with chlorpromazine, 1.25-5 mg/kg, p.o., the durations of loss of the righting reflex induced by thiopental-Na were extended in a dose-dependent manner. 3) In the mice and rats when HR-592 was administered at doses of 3-100 mg/kg, p.o., catalepsy was induced in a dose-dependent manner. 4) The incidence of catalepsy induced by haloperidol in mice was reduced dose-dependently after HR-592 administration (10-100 mg/kg, p.o.). 5) Dose-dependent suppressions of the slant of screen at which the mice slipped down were observed by HR-592 at 3-100 mg/kg, p.o., and chlorpromazine at 5-20 mg/kg, p.o. 6) The rotarod performance in mice was suppressed dose-dependently by HR-592, 3-100 mg/kg, p.o., and chlorpromazine, 5-20 mg/kg, p.o. 7) HR-592 at doses of 0.3-3 mg/kg, i.p., suppressed dose-dependently the turning behavior induced by methamphetamine in unilateral substantia nigra-lesioned rats. From these results and our previous data, it is considered that HR-592 has pharmacological properties as a major tranquilizer, although its behavioral effect is slightly weaker than that of chlorpromazine. Furthermore, these results imply that HR-592 has anti-cataleptogenic activity and might thereby alleviate the adverse effect of neuroleptics such as haloperidol.

Anesthetics↗
PubMed1990

Effects of methamphetamine on regional cerebral glucose utilization in rats with unilateral lesion of substantia nigra.

In rats with electrocoagulation of the unilateral substantia nigra (SN), methamphetamine at doses of 2.5 and 5 mg/kg, i.p., induced ipsilateral turning towards the lesioned side and caused an imbalance of the regional cerebral glucose utilization (CGU) in the caudate-putamen (CP), frontal cortex (FC) and ventromedial thalamic nucleus (VMT); i.e., showing a higher contralateral CGU as compared with the SN lesioned side. These results induced in unilateral SN-lesioned rats may be accompanied by an imbalance of neural activity in CP, FC and VMT of these rats.

Animals↗
PubMed1990

Influence of emotional stress on pharmacokinetics of isosorbide dinitrate intraperitoneally administered to rats.

The plasma level of isosorbide dinitrate intraperitoneally administered to rats stressed by foot-shock was almost the same as that in non-stressed control rats. However, levels of its metabolites, 5-isosorbide mononitrate and 2-isosorbide mononitrate, were lower in stressed rats than in non-stressed rats, suggesting that stress may influence the metabolism and/or excretion of the metabolites.

Animals↗
PubMed1990

[Liquid crystal thermography; a reliable method for detecting soda lime exhaustion].

The dynamic and functional state of soda lime can be more precisely assessed by measuring changes in wall temperatures of the absorption chambers rather than observing color change of the soda lime granules. We demonstrated in this report that the liquid crystal thermometer is an inexpensive and reliable measuring device for this purpose.

Anesthesiology↗
PubMed1989

Isolation and sequencing of a cDNA clone encoding 107 kDa sialoglycoprotein in rat liver lysosomal membranes.

A cDNA for 107 kDa sialoglycoprotein (LGP 107), the major protein component of rat liver lysosomal membranes, was isolated and sequenced. The 1.8 kbp cDNA contained an open reading frame encoding a polypeptide consisting of 386 amino acid residues (Mr 41,914). The deduced NH2-terminal 10-residue sequence is identical with that determined for purified LGP 107. The primary structure deduced for LGP 107 contains 20 potential N-glycosylation sites and exhibits 82.5, 43 and 60% sequence similarities to mouse LAMP-1, chicken LEP 100, and a 120-kDa human lysosomal glycoprotein, respectively. Among these lysosomal glycoproteins, the amino acid sequence of the putative transmembrane segment is highly conserved. Northern blot hybridization analysis identified a single species of LGP 107 mRNA (2.1 kbp in length) in rat liver, kidney, brain, lung, spleen, heart and pancreas, although its level in pancreas was very low.

Amino Acid Sequence↗
PubMed1989

Evidence that aspartic proteinase is involved in the proteolytic processing event of procathepsin L in lysosomes.

Our recent studies have shown that cathepsin L is first synthesized as an enzymatically inactive proform in endoplasmic reticulum and is successively converted into an active form during intracellular transport and we postulated that aspartic proteinases would be responsible for the intracellular propeptide-processing step of procathepsin L accompanied by the activation of enzyme (Y. Nishimura, T. Kawabata, and K. Kato (1988) Arch. Biochem. Biophys. 261, 64-71). To better understand this proposed mechanism, we investigated the effect of pepstatin, a potent inhibitor of aspartic proteinases, on the intracellular processing kinetics of cathepsin L analyzed by pulse-chase experiments in vivo with [35S]methionine in the primary cultures of rat hepatocytes. In the pepstatin-treated cells, the proteolytic conversion of cellular procathepsin L of 39 kDa to the mature enzyme was significantly inhibited and considerable amounts of proenzyme were found in the cell after 5-h chase periods. Further, the subcellular fractionation experiments demonstrated that the intracellular processing of procathepsin L in the high density lysosomal fraction was significantly inhibited and that considerable amounts of the procathepsin L form were still observed in the light density microsomal fraction after 2 h of chase. These results suggest that pepstatin treatment caused a significant inhibitory effect on the intracellular processing and also on the intracellular movement of procathepsin L from the endoplasmic reticulum to the lysosomes. These findings provide the first evidence showing that aspartic proteinase may play an important role in the intracellular proteolytic processing and activation of lysosomal cathepsin L in vivo. Therefore, we suggest that cathepsin D, a major lysosomal aspartic proteinase, is more likely to be involved in this proposed model in the lysosomes.

Animals↗
PubMed1989

Nicotine-induced tail-tremor and drug effects.

Tail-tremor induced by repeated and daily administration (0.5 mg/kg SC x 6 times/day) of nicotine as well as effects of various drugs on this response were investigated in Wistar strain male rats. Daily administration of nicotine in doses of 0.5 mg/kg SC caused tail-tremors to appear beginning on the 3rd day. Tail-tremor induced by the first injection of each day gradually increased with the daily injections, however, the heightened effect of this first injection at the beginning of each day decreased during the day upon repeated administration of 6 times/day at 2-hr intervals. Basically, tail-tremor appeared about 5 min after SC administration of nicotine and reached a peak approximately 7-9 min after injection, declining to zero afterwards. Different drugs showed various effects on this response. While mecamylamine (0.5 and 1.0 mg/kg IP) abolished nicotine-induced tail-tremor, arecoline (0.5 and 1.0 mg/kg IP), atropine (2.5 and 5.0 mg/kg IP), scopolamine (1.0 and 2.0 mg/kg IP) and hexamethonium (0.5 and 1.0 mg/kg IP) showed no such effects. Furthermore, physostigmine (0.1 mg/kg IP) actually potentiated this action. These results suggest that tail-tremor induced by nicotine may be mediated through central nicotine receptor system.

Animals↗
PubMed1989

Morphological localization of a major lysosomal membrane glycoprotein in the endocytic membrane system.

We have raised specific polyclonal immunoglobulin G (IgG) against a major lysosomal membrane sialoglycoprotein (LGP107) taken from rat liver and have prepared a conjugate of its Fab' fragment with horseradish peroxidase (HRP-anti LGP107 Fab') as a probe for the subcellular antigen. Electron immunocytochemistry in primary cultured rat hepatocytes showed that LGP107 resided primarily within lysosomes and was associated with luminal amorphous materials as well as limiting membranes. In addition, LGP107 was shown to be substantially distributed throughout the endocytic vacuolar system. The glycoprotein was found clustered in coated pits at the cell surface and localized along the surrounding membranes in endocytic vesicles. When cultured cells were exposed to HRP-anti LGP107 Fab', the antibody which was bound to its antigen within the coated pits was internalized via a system of endocytic vesicles and transported to lysosomes. During 20 min of incubation at 37 degrees C, the HRP tracer appeared at an early stage in small vesicles and moved progressively to larger vesicles, including multivesicular bodies. After 1 h, the tracer could be clearly seen in lysosomes heterogeneous in shape and size. The existence of LGP107 in endocytic compartments and the uptake of anti LGP107 antibody by hepatocytes were not blocked by prior treatment of the cells with cycloheximide and excess amounts of anti LGP107 IgG. These data suggest that LGP107 circulates between the cell surface and lysosomes through the endocytic membrane traffic in hepatocytes.

Animals↗
PubMed1989

Biochemical analysis of the movement of a major lysosomal membrane glycoprotein in the endocytic membrane system.

HRP-anti LGP107Fab' and 125I-anti LGP107IgG were used as probes to study the movement of LGP107 in the endocytic membrane transport system in primary cultured hepatocytes of rats. Following the addition of HRP-anti LGP107Fab' to the culture medium, the transfer of the antibody conjugate from the cell surface of lysosomes was examined by cell fractionation on Percoll density gradients. The HRP tracer showed a bimodal subcellular distribution, in plasma membrane and lysosomal fractions. The amount of HRP found in the lysosomal fractions became larger as the period of cell incubation was increased. The rate of HRP accumulation in lysosomes was 0.13% of the administered load per hour per 10(6) cells. When cells were given 125I-anti LGP107 IgG, the antibody was not stored but was rapidly degraded in the lysosomes. The uptake of 125I-IgG by the cells, which was assessed by measuring the TCA-soluble radiolabeled degradation products released into the medium, increased proportionally to the administered concentration of the antibody and to the incubation time. The rate of uptake of the polyvalent 125I-IgG was comparable to that for the uptake of the monovalent HRP-Fab', and remained unchanged even after long exposure of the cells to a saturating concentration of the polyvalent IgG. This uptake process continued for many hours in the cells exposed to the protein synthesis inhibitor, cycloheximide. These results suggest that there is a continuous circulation of LGP107 between the cell surface and lysosomes in hepatocytes.

Animals↗
PubMed1989

Influences of psychological stress produced by intraspecies emotional communication on nicorandil plasma levels in rats.

Influences of emotional stress on nicorandil pharmacokinetics were studied in rats that received physical and psychological stimuli (referred to as 'sender' and 'responder' rats, respectively) using the communication box paradigm. Concerning pharmacokinetic, there was no marked difference in the Tmax, Ka, Kel, T1/2 and Vd between the sender rats and the nonstressed control rats when both of which were orally administered 10 mg/kg of nicorandil. But the Cmax and AUC were lower and clearance (Cl) was higher in the sender rats. In the responder rats, there was no difference in Tmax, Ka, Kel, and T1/2. But the Cmax and AUC were lower and the Vd was higher than those of the control rats. On the other hand, when nicorandil was administered in a dose of 5 mg/kg subcutaneously, Tmax and T1/2 in the sender rats did not differ from those of the controls, but the Cmax, Ka and AUC were lower, and the Kel, Vd and Cl were higher. Between the responder and control rats, significant differences were found in all parameters except for Vd, i.e., Cmax, Ka, T1/2 and AUC were lower than those of control rats, and the Tmax, Kel and Cl were higher than those of control rats. This indicates that pharmacokinetics of nicorandil when administered orally and subcutaneously were influenced not only by physical stress but also by psychological stress.

Animal Communication↗