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Biomedical subjects

K Konno

Publications and source records attributed to K Konno.

At least 19 recordsLinked to original sources
PubMed1992

Effects of alkyl substitutions of xanthine skeleton on bronchodilation.

Structure-activity relationships in a series of 1,3,7-trialkyl-xanthine were studied with guinea pigs. Relaxant actions in the tracheal muscle were increased with alkyl chain length at the 1- and 3-positions of the xanthine skeleton, but decreased by alkylation at the 7-position. Positive chronotropic actions in the right atrium were potentiated with 3-alkyl chain length but tended to decrease with 1-alkylation and diminish by 7-substitution. Consequently, while the 1- and 3-substitutions were equally important for the tracheal smooth muscle relaxation, the substitution at the 1-position was more important than the 3-substitution for bronchoselectivity. The 7-alkylation may be significant to cancel heart stimulation. There were good correlations between the smooth muscle relaxant action and the cyclic AMP-PDE inhibitory activity in 3-substituents and the affinity for adenosine (A1) receptors in 1-, 3-, and 7-substituents. This suggests that not only the cyclic AMP-PDE inhibitory activity but also the adenosine antagonistic activity is important in the bronchodilatory effects of alkylxanthines. Among these xanthine derivatives, 1-butyl-3-propylxanthine and its 7-methylated derivative showed high bronchoselectivity in the in vitro and in vivo experiments compared to theophylline and enprofylline and may be new candidates for bronchodilator.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Effects of angiotensin II and angiotensin III on airway epithelial short-circuit current: involvement of pertussis toxin-sensitive G protein.

The effects of angiotensin II (AII) and angiotensin III (AIII) on bioelectric properties of canine cultured tracheal epithelium were investigated. Both peptides increased the short-circuit current (Isc), an effect that was accompanied by the release of prostaglandin (PG) E2 and was abolished by indomethacin and diphenylamine-2-carboxylate but not by amiloride. The AII action was not altered by amastatin. The increases in Isc induced by AII and AIII were inhibited by pertussis toxin, whereas cholera toxin had no effect. Thus, both peptides may selectively stimulate airway epithelial Cl- secretion through the activation of pertussis toxin-sensitive regulatory G protein and the subsequent generation of PGE2.

Angiotensin II↗
PubMed1992

Angiotensin II potentiates neurally mediated contraction of rabbit airway smooth muscle.

The effect of angiotensin II (AT II) on cholinergic neurotransmission in rabbit tracheal segments was studied under isometric conditions in vitro. AT II concentration-dependently potentiated the contractile response to electrical field stimulation (EFS), and caused a leftward shift of the frequency-response curves for EFS, so that the stimulus frequency required to produce a half-maximal effect (ES50), decreased from 7.0 +/- 0.1 to 3.0 +/- 0.1 Hz (P less than 0.01). In contrast, the contractile response to acetylcholine was not affected. Non-peptide AT II receptor antagonist CV-2961 attenuated the effect of AT II on the EFS-induced contraction. Pretreatment of tissues with thiorphan or phosphoramidon did not alter the action of AT II. Thus, AT II may prejunctionally potentiate the neurally-mediated contraction of airway smooth muscle through activation of AT II receptors on the cholinergic nerve terminals, and this effect may not be modulated by endogenous neutral endopeptidase.

Angiotensin II↗
PubMed1992

Thromboxane A2 mimetic U46619 stimulates ciliary motility of rabbit tracheal epithelial cells.

To elucidate whether thromboxane A2 (TxA2), one of the important arachidonic acid metabolites that may play a role in the development of airway inflammation, affects respiratory ciliary motility and, if so, what the mechanism of action is, we measured ciliary beat frequency (CBF) of rabbit cultured tracheal epithelium in response to U46619, a TxA2 mimetic agonist, by a photoelectric method. Addition of U46619 (10(-5) M) increased CBF from 17.7 +/- 0.7 to 22.8 +/- 1.4 Hz (mean +/- SE, p less than 0.01) within 5 min, which was followed by a decline to the baseline value by 10 min. This effect was concentration-dependent, the maximal increase from the baseline value and the drug concentration required to produce a half-maximal effect (EC50) being 26.9 +/- 4.6% (p less than 0.01) and 3 x 10(-7) M, respectively. The U46619-induced increase in CBF was abolished by SQ29548, and TxA2 receptor antagonist, and inhibited by verapamil, a Ca(2+)-entry blocker, and H-7, a protein kinase C inhibitor. These results suggest that TxA2 stimulates ciliary motility through the activation of airway epithelial TxA2 receptors, and that this effect may be exerted from Ca(2+)-influx and protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Prostaglandin D2 increases Cl secretion across canine tracheal epithelium through cyclo-oxygenase stimulation and cAMP production.

Prostaglandin (PG) D2 is one cyclo-oxygenase product of arachidonic acid metabolites that may play a role in the pathogenesis of asthma. To determine the effect of PGD2 on ion transport by airway epithelium and its mechanism of action, we measured bioelectric properties of canine cultured tracheal epithelium under short-circuit conditions in vitro. PGD2 (10(-7) M) increased short-circuit current (Isc) from 5.5 +/- 1.2 to 14.1 +/- 2.9 microA cm-2 (means +/- SE, P less than 0.01) when added to the mucosal solution, and to 22.2 +/- 3.8 microA cm-2 (P less than 0.001) when added to the submucosal solution, an effect that was accompanied by the corresponding increases in transepithelial potential difference and conductance. These effects were dose-dependent. The PGD2-induced increase in Isc was not altered by preincubation of cells with autonomic antagonists (phentolamine, propranolol, atropine), the lipoxygenase inhibitor AA-861, the protein kinase C inhibitor H-7, or the Na channel blocker amiloride, but it was inhibited by each of indomethacin, piroxicam, the Cl channel blocker diphenylamine-2-carboxylate, the Cl transport inhibitor furosemide, and Cl-free medium. Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels were dose-dependently increased by PGD2. These results suggest that PGD2 may selectively stimulate airway epithelial Cl secretion via cyclo-oxygenase- and cAMP-dependent pathway.

Animals↗
PubMed1992

Selective bronchodilators from 1-(5'-oxohexyl)xanthines.

A series of twenty one 1-(5'-oxohexyl)xanthines substituted with alkyl chains at the N3 and N7 positions of the xanthine nucleus were prepared and their relaxant activity in guinea-pig isolated tracheal muscle and positive chronotropic activity in isolated right atrium of guinea-pig were compared. The tracheal relaxant activities were markedly increased with alkyl chain length at the N3 position, but decreased by the N7 alkylation. The positive chronotropic activities in the right atrium were increased by introduction of an n-propyl group at the N3 position but decreased by substitution of longer alkyl chains, and the action on the heart was diminished by N7 substitution. The activities of compounds on cAMP-phosphodiesterase (PDE) and binding of [3H]8-cyclopentyl-1,3-dipropylxanthine were measured in the homogenate of tracheal muscle and the membrane preparation of cerebral cortex, respectively. No relationship among tracheal muscle relaxant activity, cAMP-PDE inhibitory activity and adenosine antagonism of these xanthines was observed, and other action mechanisms should be considered for their relaxant activities. This study indicated that N3 alkylation is important for the selectivity for tracheal muscle, while the introduction of long alkyl chains such as n-butyl and n-pentyl groups at the N3 and N7 positions diminished the potency for the right atrium in guinea-pigs. 3-n-Pentyl- and 7-methyl-3-n-pentyl-1-(5'-oxohexyl)xanthines showed much higher bronchoselectivity than oxpentifylline and theophylline.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Abnormal movement of the arytenoid region as a cause of upper airway obstruction.

A 75 year old woman presented with a three week history of severe dyspnoea and cough. Auscultation and spirometry suggested extrathoracic inspiratory airway obstruction, and bronchoscopy showed abnormal motion of the arytenoid region (supraglottic area), causing upper airway obstruction only during forced inspiratory efforts. Sedatives improved the symptoms within a week. It is suggested that reversible malfunction of the arytenoid region can be responsible for upper airway obstruction.

Aged↗
PubMed1992

Stimulation of Cl secretion by lactoferrin across canine airway epithelial cells in culture.

To investigate the effect of lactoferrin, an iron-binding glycoprotein in the respiratory tract, on ion transport function of airway epithelial cells, we measured bioelectric properties of canine cultured tracheal epithelium by Ussing's short-circuit technique. Addition of lactoferrin (60 micrograms/ml) to the mucosal side of epithelial sheet increased the short-circuit current (Isc) from 4.8 +/- 0.8 to 7.5 +/- 1.1 microA/cm2, and the submucosal addition likewise increased Isc from 3.8 +/- 0.6 to 5.6 +/- 0.7 microA/cm2 (p < 0.001, in each case). This effect was concentration dependent. The lactoferrin-induced increase in Isc was not altered by amiloride, indomethacin, or propranolol but was abolished by diphenylamine-2-carboxylate or substitution of Cl with iodide in the medium. Intracellular cyclic AMP levels were not increased by lactoferrin. These results suggest that lactoferrin may selectively stimulate Cl secretion across the airway mucosa, an effect that may not be dependent on prostaglandins, beta-adrenergic receptor or intracellular cyclic AMP.

Animals↗
PubMed1992

Anterotracheal temperature during and after exercise in the guinea pig.

We measured the temperature in the anterotracheal region of the guinea pig during and after various intensities of exercise (from 20 to 100 m/3 min). The temperature decreased during exercise, and the maximal drop of the temperature increased with increasing intensity of exercise up to a speed of 80 m/3 min. When the exercise was discontinued, the temperature initially fell rapidly, then rose progressively to equal or exceed the preexercise value. The changes in temperature were similar among 5 animals. These findings suggest that the tracheal wall temperature changes during and after exercise relative to the intensity of exercise. Using this method in guinea pigs may provide more information about the pathophysiology of exercise-induced asthma.

Animals↗
PubMed1992

Angiotensin II-1 receptor-mediated Cl secretion by canine tracheal epithelium.

To elucidate the effect of angiotensin II (AII) on ion transport function of airway epithelium, we studied the bioelectrical properties of canine cultured tracheal epithelium under short-circuit conditions in vitro. Addition of AII to submucosal solution in Ussing chambers increased the short-circuit current (ISC) in a dose-dependent fashion, the maximal increase from the baseline value and the concentration required to produce a half-maximal effect being 5.2 +/- 0.5 microA/cm2 (p < 0.001) and 10(-6) M, respectively. In contrast, mucosal AII had little effect. The AII-induced increase in ISC was not altered by the AII-2 receptor antagonist EXP655 but was depressed by the AII-1 receptor antagonist DuP 753. Diphenylamine-2-carboxylate, Cl-free medium, indomethacin, the phospholipase A2 inhibitor mepacrine, and the methyltransferase inhibitor 3-deazaadenosine reduced the change in ISC, whereas amiloride and the lipoxygenase inhibitor AA-861 did not. Addition of AII to the submucosal but not the mucosal side increased the release of prostaglandin E2, an effect that was abolished by DuP 753. These results suggest that AII may interact with the submucosal AII-1 receptor and stimulate Cl secretion across tracheal epithelium through the mobilization of arachidonic acid and the release of prostaglandin E2.

Angiotensin II↗
PubMed1992

Lignified materials as medicinal resources. V. Anti-HIV (human immunodeficiency virus) activity of some synthetic lignins.

A class of synthetic lignins (dehydrogenation polymers of p-coumaric acid, ferulic acid, and caffeic acid) inhibited cytopathogenicity of HIV-1 and HIV-2 infection. The ratio of cytotoxic to anti-HIV (human immunodeficiency virus) doses depended strongly on conditions during polymer preparation. The activity increased when polymers were treated with reducing agent NaBH4, whereas it decreased when treated with oxidizing agent ceric ammonium nitrate. The polymers inhibited expression of HIV-specific antigen in the infected cells and also inhibited HIV-binding to the cells, but not completely, even at doses that almost completely inhibited the HIV-induced cytopathogenic effect. These results suggest that lignin structure, regardless of whether synthetic or natural, may inhibit HIV replication by an unidentified process, and thus prove to be a new class of anti-HIV agents possibly effective in the treatment of AIDS (acquired immunodeficiency syndrome).

Antiviral Agents↗
PubMed1992

Stimulation of Na absorption by the antiasthmatic kampo drug Saiboku-to in cultured airway epithelium.

To study the effect of the Kampo drug Saiboku-to (TJ-96) on ion transport function of airway epithelial cells, we studied bioelectric properties of cultured tracheal epithelium from dogs under short-circuit conditions in vitro. Addition of TJ-96 (1 mg/ml) to the mucosal solution of the Ussing chamber increased the epithelial short-circuit current (SCC) from 6.5 +/- 0.7 to 11.4 +/- 1.6 microA/cm2 (P less than 0.001). This effect was dose-dependent, with the maximal increase from the baseline value and the concentration required to produce a half-maximal effect (EC50) being 70.5 +/- 12.6% (P less than 0.001) and 3 micrograms/ml, respectively; and there were corresponding increases in transepithelial potential difference and cell conductance. Submucosal addition of TJ-96 likewise increased SCC, although the magnitude of the response was smaller as compared with the response to the mucosal addition. The TJ-96-induced increase in SCC was not affected by diphenylamine-2-carboxylate or furosemide but abolished by amiloride. Intracellular cyclic AMP levels were dose-dependently increased by TJ-96. These results indicate that TJ-96 may selectively stimulate Na absorption across the tracheal epithelium, probably through intracellular accumulation of cyclic AMP.

Animals↗
PubMed1992

Lung cancer in patients with idiopathic pulmonary fibrosis.

We investigated lung cancer in 99 patients with idiopathic pulmonary fibrosis (IPF). Lung cancer was found in 31 (31.3%) of 99 patients with IPF. Most (87.9%) tumors, including squamous cell carcinoma, were observed in the peripheral region of the lung, whereas the distribution of histologic types of cancers was similar to that seen in ordinary lung cancer. Peripheral tumors were frequently seen in the lower lobe, where fibrotic shadow was prominent. However, the severity of fibrosis was not related with the prevalence or histologic type of lung cancer. Two-thirds of IPF patients having a smoking history of over 40 years developed lung cancer. When compared with nonsmoking IPF control subjects, the relative risk of smoking in IPF patients was 3.5, identical with that reported for smokers in the general population. We suggest that smoking in patients with IPF is an additive risk factor for the development of lung cancer. We also speculate that the high prevalence of peripheral squamous cell carcinoma might be associated with cigarette smoking.

Aged↗
PubMed1992

Multiple forms of mammalian sialidase: altered expression in carcinogenesis.

We have demonstrated that rat liver contains at least four types of sialidase differing in subcellular location, in catalytic property and immunologically. They are intralysosomal, cytosolic and membrane-associated sialidases I and II. Membrane sialidase I locates mainly in plasma membrane and sialidase II in lysosomal membrane. Immunological study reveals that the same types of sialidase exist in various tissues of rat and of other mammalian species. Based on these results, we examined the sialidases in rat hepatomas and in transformed cells of JB6 mouse epidermal cell. Hepatomas were found to possess four types of sialidase and the three of them altered quantitatively. Intralysosomal sialidase activity was higher but cytosolic and lysosomal membrane sialidase activities were lower in hepatomas than in control liver. When the sialidases of transformants of JB6 cells were compared with those of control cells, the activities of two lysosomal sialidases were decreased and contrarily plasma membrane sialidase was increased. We discussed a possible significance of the sialidase alterations in carcinogenesis.

Animals↗
PubMed1992

[Effect of diaphragmatic fatigue on ventilatory response to carbon dioxide].

To clarify the effect of respiratory muscle fatigue on ventilatory response to carbon dioxide, we performed CO2 rebreathing study before and after diaphragmatic fatigue in nine healthy males. Diaphragmatic fatigue was induced by inspiratory resistor loading and confirmed by the increase in Tension Time Index and the decrease in Pdi max at FRC. The effects of diaphragmatic fatigue were as follows: 1) S and B value of VE-CO2 curve did not change. 2) P1-CO2 curve shifted to the left but the slope of the curve did not change. 3) delta Ppl response to CO2 decreased, but delta Pdi response to CO2 did not change. 4) The increase in respiratory accessory muscle EMG was more prominent, compared to diaphragmatic EMG. 5) Rib cage movement became more marked. In conclusion, diaphragmatic fatigue (with 60 percent decrease in Pdi max at FRC) does not affect on ventilatory response to carbon dioxide. To maintain the homeostasis of the chemical ventilatory feedback system, diaphragmatic dysfunction is compensated by the increased activity of respiratory accessory muscles with possible increase in neural drive.

Adult↗
PubMed1992

[Effects of angiotensin peptides on airway epithelial ion transport and its modulation by angiotensin converting enzyme].

To study the effects of angiotensin (ANG) peptides on airway epithelial ion transport function, we evaluated the bioelectric properties of canine cultured tracheal epithelium under short-circuit conditions in vitro. Addition of ANG I, II and II dose-dependently increased short-circuit current (Isc) and transepithelial potential difference, an effect that was more pronounced with addition to the submucosal solution than to the mucosal solution, with rank order of potency of ANG II greater than or equal to ANG II much greater than ANG I. The ANG-induced increase in Isc was not altered by the Na channel blocker amiloride, but was greatly reduced by the CI channel blocker diphenylamine-2-carboxylate and Cl-free medium. The response of Isc to ANG I was reduced by MK422, an angiotensin converting enzyme inhibitor, in a dose-dependent fashion. These results suggest that ANG II and III selectively stimulate Cl secretion across airway epithelium and that ANG I may exert its effect after its conversion to ANG II by angiotensin converting enzyme.

Angiotensin I↗