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Biomedical subjects

K Kurihara

Publications and source records attributed to K Kurihara.

At least 145 records · Page 8Linked to original sources

Cholinergic differentiation of cultured sympathetic neurons induced by retinoic acid. Induction of choline acetyltransferase-mRNA and suppression of tyrosine hydroxylase-mRNA levels.

Here we show that retinoic acid (RA) has the ability to alter the transmitter phenotype of cultured sympathetic neurons from newborn rats superior cervical ganglia (SCG). In the presence of RA, the level of choline acetyltransferase (ChAT) mRNA was increased, while the level of tyrosine hydroxylase (TH) mRNA was reduced in the cultured SCG neurons. Selective PCR amplification of different upstream regions of the ChAT-mRNA indicates that RA promotes the transcription of ChAT gene from R and M exons. The RA-induced upregulation of ChAT-mRNA level was significantly diminished by the chronic treatment with phorbol ester, suggesting that PKC has an important role in the induction of ChAT-mRNA in this system.

Animals↗

Receptor mechanisms of bitter substances.

The receptor mechanism of bitter substances was discussed from the following points of views. (a) Both electrostatic and hydrophobic interactions of bitter substances with taste receptor membranes contribute to reception of bitter substances having a positive charge. (b) In the frog, the responses to bitter substances are easily adapted. The presence of Ca ion in the medium prolongs the responses. (c) Bitter substances elicit electrical responses in nongustatory cells such as neuroblastoma cells and olfactory cells, suggesting that bitter substances induce the response by nonreceptor-mediated mechanism. (d) There is also a possibility that receptors for some bitter substances are G-protein coupled. We cloned G-protein coupled receptors from bovine taste tissues. (e) A specific inhibitor of bitter taste has been desired in pharmaceutical and food sciences, but it has not been available. We found that a lipoprotein made of phosphatidic acid and beta-lactoglobulin selectively inhibits the responses to bitter substances in the frog and humans. Binding of the lipoprotein to the receptor sites for bitter substances leads to suppression of the response.

Amino Acid Sequence↗

Forskolin enhanced off-response in the turtle olfactory system.

Olfactory responses appear not only at the onset of odor stimulation, but also at the termination of the stimulation. It is widely considered that the cAMP-pathway is involved in the generation of odor responses. We examined how cAMP affects the generation of off-responses. To explore the role of the cAMP-pathway, odorants were applied to the turtle olfactory epithelium after forskolin at high concentrations which saturated the olfactory response to forskolin. Various odorants induced off-responses after 50 microM forskolin, indicating that off-responses are not induced via the cAMP-dependent pathway. However, the magnitude of the off-response after forskolin varied from 100 to 1400% of those of off-responses in its absence, indicating that forskolin greatly enhanced the off-responses to some odorants. The off-response after 0.1 mM citralva was also enhanced by 3 mM 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (cpt-cAMP). These results suggested that cAMP modulates off-responses in the turtle olfactory system.

1-Methyl-3-isobutylxanthine↗

Effects of nerve growth factor and dexamethasone on Na+,K(+)-ATPase of cultured PC12h cells.

When PC12h cells were cultured for 4 days in the presence of 50 ng/ml of nerve growth factor (NGF), they showed elongated dendrites and specifically increased Na+,K(+)-ATPase activity. Either singly or in combination with NGF, dexamethasone also increased the specific activity of this enzyme. Western blot analysis using anti-alpha 1 and anti-alpha 2 antisera showed that PC12h cells, either before or after hormone treatment, contained the alpha 1 isoform but not the alpha 2 one. We conclude, therefore, that NGF induces Na+,K(+)-ATPase concomitantly with neuronal differentiation in PC12h cells but that the growth factor does not induce formation of the myelin sheath, which normally expresses the alpha 2 isoform of Na+,K(+)-ATPase.

Animals↗

A large contribution of a cyclic AMP-independent pathway to turtle olfactory transduction.

Although multiple pathways are involved in the olfactory transduction mechanism, cAMP-dependent pathway has been considered to contribute mainly to the transduction. We examined the degree of contribution of cAMP-independent pathway to the turtle olfactory response by recording inward currents from isolated cells, nerve impulses from cilia and olfactory bulbar responses. The results obtained by the three recordings were essentially consistent with each other, but detail studies were carried out by recording the bulbar response to obtain quantitative data. Application of an odorant cocktail to the isolated olfactory neuron after injection of 1 mM cAMP from the patch pipette elicited a large inward current. Mean amplitude of inward currents evoked by the cocktail with 1 mM cAMP in the patch pipette was similar to that without cAMP in the pipette. Application of the cocktail after the response to 50 microM forskolin was adapted also induced a large inward current. Application of the odorant cocktail to the olfactory epithelium, after the response to 50 microM forskolin was adapted, brought about an appreciable increase in the impulse frequency. The bulbar response to forskolin alone reached a saturation level around 10 microM. After the response to 50 microM forskolin was adapted, 11 species of odorants were applied to the olfactory epithelium. The magnitudes of responses to the odorants after forskolin were 45-80% of those of the control responses. There was no essential difference in the degree of the suppression by forskolin between cAMP- and IP3-producing odorants classified in the rat, suggesting that certain part of the forskolin-suppressive component was brought about by nonspecific action of forskolin. Application of a membrane permeant cAMP analogue, cpt-cAMP elicited a large response, and 0.1 mM citralva after 3 mM cpt-cAMP elicited 51% of the control response which was close to the response to citralva after 50 microM forskolin. A membrane permeant cGMP analogue, db-cGMP elicited a small response and the response to 0.1 mM citralva was unaffected by db-cGMP. It was concluded that cAMP-independent (probably IP3-independent) pathway greatly contributes to the turtle olfactory transduction.

1-Methyl-3-isobutylxanthine↗

Olfactory responses of chum salmon to amino acids are independent of large differences in salt concentrations between fresh and sea water.

In chum salmon captured at the coastal sea and the natal river, the magnitudes of the olfactory nerve responses to the amino acids after perfusion of the olfactory epithelium with artificial pond water (APW) were similar to those after perfusion with artificial sea water (ASW), although the concentrations of Na+, Cl- and Ca2+ in ASW were 986, 430 and 27 times higher than those in APW, respectively. The findings suggest that the permeability of these ions across the apical membranes of olfactory cells do not essentially contribute to the transduction mechanism in the salmon.

Amino Acids↗

Identification of mK1, a true tissue (glandular) kallikrein of mouse submandibular gland: tissue distribution and a comparison of kinin-releasing activity with other submandibular kallikreins.

The protein structure, kinin-releasing activity, and tissue distribution of four major proteinases of mouse submandibular gland (mK22, mK9, proteinase F, proteinase P) were studied. When compared with the deduced amino acid sequence of each member of the tissue (glandular) kallikrein gene family, the amino acid sequence of proteinase F determined (approximately 40% of the total) was found to agree completely with the deduced amino acid sequence of mKlk-1. The proteinase P sequence, on the other hand, agreed with that of the product of mKlk-13, mK13 (prorenin-converting enzyme). Proteinase F had the strongest kininogenase activity for both low-molecular-weight and high-molecular-weight kininogen, while mK22 had 1/6 and 1/50 the activity of proteinase F for the respective kininogen substrate. Kininogenase activities of mK9 and proteinase P were less than 1/100 of the activity of proteinase F for both substrates. Acting on the two kininogen substrates, kallikreins mK22, mK9, and proteinase F, but not proteinase P, specifically released bradykinin, suggesting that the former three kallikreins strictly recognized peptide sequences around bradykinin in these substrate molecules but proteinase P recognized several sites in these molecules. Significant amounts of proteinase F, but not mK22 and others, were present in the urine, pancreas and digestive organs, as well as in the salivary glands. The present results revealed that the former proteinase F is identical to mK1, tissue/renal kallikrein, and confirmed its characteristics as a true kallikrein on the basis of its kinin-releasing activity and tissue distribution.

Amino Acid Sequence↗

Malignant lymphoma of the esophagus associated with macroglobulinemia: report of a case.

A case of non-Hodgkin's lymphoma of the esophagus in a 74 year old man is presented. Grossly, the surgically removed esophagus had a fusiform submucosal mass covered with smooth surfaced mucosa. Microscopic examination revealed that the mass consisted of a dense infiltrate of small to medium-sized lymphoid cells with plasmacytoid differentiation, leading to a diagnosis of diffuse small cell lymphoma with lymphoplasmacytic subtype. Laboratory data as well as immunohistochemical studies proved that the lymphoma produced monoclonal immunoglobulin M, giving rise to macroglobulinemia.

Aged↗

Enhancement of canine taste responses to umami substances by salts.

The effects of salts on canine taste responses to umami substances were examined by recording the activity of the chorda tympani nerve. 1) The responses to monosodium glutamate (MSG), disodium 5'-guanylate (GMP), and that induced by the synergism between MSG and GMP were enhanced by the presence of various salts. 2) The effective salts were those carrying inorganic cations such as Na, K, and Mg, while CaCl2 had no enhancing effect. Salts carrying organic cations such as tris(hydroxymethyl)aminomethane (Tris), choline, N-methyl-D-glucamine, and 1,3-bis[tris(hydroxymethyl)-methylamino]propane also produced positive results. 3) The dependence of the umami responses on NaCl and MgCl2 concentrations showed a bell-shaped response curve with the maximal enhancing effect being seen at 100 mM NaCl and 3-10 mM MgCl2. 4) The degree of the enhancement depended not only on the species of the cation, but also on that of anion. For example, 100 mM NaCl showed a much larger enhancing effect than Na phosphate, Na2SO4, and Na4Fe(CN)6 at equimolar Na+. 5) The enhancing effects of salts on the responses to the umami substances could not be simply explained in terms of the permeability of cation and anion of salts. It was speculated that the binding of both cations and anions to the receptor membranes leads to changes in the interaction of the umami substances with the receptor proteins.

Animals↗

Temperature increase abolishes ability of turtle olfactory receptors to discriminate similar odorant.

We examined the effects of temperature changes on odor-discriminating ability of turtle olfactory receptors in vivo by applying the cross-adaptation method to the olfactory bulbar responses. The olfactory system discriminated well all eight pairs of odorants examined at 5 and 18 degrees C. The ability of the olfactory receptors to discriminate pairs of odorants having similar structures (e.g., trans-3-hexenol and cis-3-hexenol; d-carvone and l-carvone) was reversibly abolished by increasing the temperature up to 40 degrees C, whereas discrimination of odorants having quite different structures was much less affected. The membrane fluidity of cells isolated from turtle olfactory epithelia and liposomes made of lipids extracted from the epithelia changed in a similar temperature range as for the decrease of the odor-discriminating ability, suggesting that an increase in membrane fluidity is correlated with the abolishment of the odor-discriminating ability. The present results also suggest that in vivo desensitization (adaptation) occurs not at the cellular level but at the receptor level. This mechanism was supported by the data recorded from a single olfactory cilium, showing that a single cell has both receptors for l-carvone and d-carvone and that the response to d-carvone appeared after the response to l-carvone was adapted.

Amino Acids↗

Characterization of new inbred strains of Dahl-Iwai salt-sensitive and salt-resistant rats.

Dahl-Iwai salt-sensitive (S) and salt-resistant (R) rat strains were newly established as inbred strains. To characterize the strains, the Dahl-Iwai S and R rats were fed low-salt (0.3% NaCl) and high-salt (8.0% NaCl) diets from 5 weeks after birth, and systolic blood pressure and pathologic findings were examined at intervals. The distributions of alleles at 19 biochemical and immunologic loci also were examined in the aforementioned strains, together with those for the inbred SS/Sea and SR/Sea strains, which were derived from inbred SS/Jr and SR/Jr strains, respectively. The Dahl-Iwai S rats were hypertensive after 3 weeks of consuming the 8.0% NaCl diet and died from 6 to 10 weeks after the diet was initiated. Renal lesions developed after 4 weeks' consumption of the high-salt diet. The Dahl-Iwai S rats were not hypertensive until at least the age of 21 weeks while they consumed the 0.3% NaCl diet, whereas it was reported that the SS/Jr rats became hypertensive at about 20 weeks of age when they consumed the low-salt diet. The Dahl-Iwai R rats were normotensive whether fed the 0.3 or 8.0% NaCl diet. Hydronephrosis was not observed in the Dahl-Iwai R rats, though it develops in SR/Jr rats with high frequency. Different distributions were detected for kidney alkaline phosphatase-1 (Akp-1) and amylase-1 (Amy-1) alleles between the Dahl-Iwai S and SS/Sea strains, and for esterase-14 (Es-14) and seminal vesicle protein-1 (Svp-1) alleles between the Dahl-Iwai R and SR/Sea strains. The phenotypic differences between the substrains of inbred Dahl rats could be ascribed to different genetic backgrounds.

Aging↗

Discrimination of odorants in the non-olfactory system: analysis of responses of the frog gustatory system to odorants by multidimensional scaling.

The ability of the bullfrog gustatory system to discriminate odorants was examined by the cross-adaptation technique. Application of various odorants to the tongue increased the frequency of impulses of the gustatory nerve. The magnitude of the response to the second odorant, after the response to the first odorant was adapted, varied greatly with combination of odorants. Analysis of data obtained by a multidimensional scaling suggests that the ability of the frog gustatory system to discriminate odorants is similar to that of the human olfactory system.

Adaptation, Physiological↗

[Three cases of typical cryptomeria pollen asthma].

We treated three asthmatic children diagnosed as typical cryptomeria pollen asthma (Cryptomeria japonica). Wheezing started from one to four years after onset of pollinosis. Asthmatic attacks occurred one or several days after pollen counts increased. We could find asthmatic attacks in the years when the pollen counts were higher than in average years. In the laboratory findings, only specific IgE antibody to cryptomeria with its high titer of over 17.5 PRU/ml was detected in these three cases. Allergen inhalation tests were performed with positive results in the two cases, suggesting that these three cases were typical child cryptomeria pollen asthma.

Adult↗

Induction of cholinergic and adrenergic differentiation in N-18 cells by differentiation agents and DNA demethylating agents.

Effects of various differentiating agents and DNA demethylating agents on the expression of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH), marker enzymes for cholinergic and adrenergic differentiation, respectively, were examined in N-18 neuroblastoma cells. Retinoic acid (RA) and a medium conditioned over C6-glioma cells (GCM), which have been shown to enhance the ChAT activity of PC12 cells, NG108-15 cells and fetal rat brain cells, did not induce ChAT activity of N-18 cells. Treatment of the cells with the DNA demethylating agents alone also did not affect ChAT activity. But after pretreatment of the cells with the DNA demethylating agents, ChAT activity of N-18 cells was greatly increased by either RA or GCM. TH activity of N-18 cells was enhanced by forskolin, an activator of adenylate cyclase. The pretreatment of the cells with the DNA demethylating agents greatly enhanced the induction of TH activity by forskolin. Levels of ChAT and TH messenger RNA were altered in accordance with changes in ChAT and TH activities. Possible mechanisms of the actions of the demethylating agents on cholinergic and adrenergic differentiation are discussed.

Acetylcholine↗

Identification of novel members of G-protein coupled receptor superfamily expressed in bovine taste tissue.

Using reverse transcription-polymerase chain reaction (RT-PCR) and degenerate oligonucleotide primers, we amplified novel members of two different subfamily of G-protein coupled receptor (GCR) superfamily from bovine taste tissue. Type A receptor clones composed of multiple cDNA clones had significant similarity with putative olfactory receptor subfamily, while a single type B clone had significant similarity with peptide receptor subfamily. Physiological functions of these receptors in taste cells are discussed.

Amino Acid Sequence↗

Weak N activity of En(a-) human erythrocyte membranes.

The propositus's erythrocytes with phenotype En(a-), which was found for the first time in a Japanese family, reacted more weakly with anti-N serum than the ordinary phenotype N erythrocytes. The En(a-) erythrocytes lack the major membrane sialoglycoprotein (glycophorin A) as demonstrated by Bio-Gel 1.5m gel filtration from active sialoglycoproteins, which were isolated from En(a-) erythrocyte membranes by the method of lithium diiodosalicylate (LIS)-phenol extraction. It is suggested from observation via enzyme-linked immunosorbent assay (ELISA) that N activity is derived from the glycophorin B molecule on En(a-) erythrocyte membranes.

Antigens↗