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Biomedical subjects

K Konno

Publications and source records attributed to K Konno.

At least 217 records · Page 12Linked to original sources
PubMed1993

[Effect of bradykinin on airway epithelial ion transport and its modulation by endogenous peptidases].

To elucidate the effect of bradykinin (BK) on airway epithelial ion transport function and its modulation by endogenous peptidases, we studied the electrical properties of canine cultured tracheal epithelium under short-circuited conditions in vitro. Addition of BK to the mucosal side of Ussing chamber increased short-circuit current (SCC) in a dose-dependent manner, the maximal rise from the baseline value (delta SCC max) and the concentration required to produce a half-maximal effect being 7.1 +/- 0.7 microA/cm2 (p < 0.001) and 3.9 +/- 1.0 x 10(-7) M, respectively. This effect was greatly attenuated by the B2-receptor antagonist (D-Arg, Hyp3, Thi5,8, d-Phe7)-BK but not by the B1-receptor antagonist (Des-Arg9, Leu8)-BK. Blockade of angiotensin converting enzyme and aminopeptidase P by captopril and mercaptoethanol did not alter the BK-induced increase in SCC. On the other hand, phosphoramidon and MERGAPTA, inhibitors of neutral endopeptidase and carboxypeptidase N, respectively, strengthened the effect of BK. These results suggest that BK stimulates airway epithelial electrical properties through the activation of B2-receptor subtype, and that endogenous peptidases including neutral nedopeptidase and carboxypeptidase N may play a modulatory role in this action of BK.

Animals↗
PubMed1993

Lesions of the arytenoid region in a patient with exertional dyspnoea.

A 63 year old woman presented with a 3 year history of exertional dyspnoea. Spirometry suggested extrathoracic airway obstruction (decreased inspiratory flow and saw-tooth pattern of flow-volume curves), and bronchoscopy revealed structural lesions and a trembling motion in the arytenoid region, causing upper airway obstruction on forced respiratory efforts. As there were no abnormal findings other than the lesions, the exertional dyspnoea was probably caused by impaired movement of the arytenoid region.

Dyspnea↗
PubMed1993

Role of Na(+)-K(+)-ATPase in airway smooth muscle relaxation by vasoactive intestinal peptide and pituitary adenylate cyclase activating peptide.

To elucidate the effects of vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) on airway smooth muscle function, we studied rabbit isolated tracheal segments under isometric conditions in vitro. Addition of VIP and PACAP dose-dependently relaxed tracheal smooth muscle precontracted with acetylcholine, with the order potency being PACAP (1) > or = VIP (0.78), accompanied by the corresponding increase in intracellular cyclic AMP levels. The VIP- and PACAP-induced muscle relaxations were significantly inhibited by ouabain and K(+)-free medium. Incubation of tissues with VIP reduced the contractile responses to electrical field stimulation, whereas PACAP had no effect. These results suggest that VIP and PACAP may cause bronchodilation through activation of Na(+)-K(+)-ATPase and that VIP but not PACAP inhibits the release of acetylcholine from the cholinergic nerve terminals.

Acetylcholine↗
PubMed1993

[Inhibitory effect on sulfur dioxide on ciliary motility in rabbit tracheal epithelium and its prevention by intracellular cyclic AMP].

To elucidate the role of endogeneous cyclic AMP in the protection against airway mucosal dysfunction induced by air pollutants, we studied the effect of sulfur dioxide (SO2) on ciliary motility in rabbit cultured tracheal epithelium in vitro. Exposure of cells to perfusate bubbled with SO2 rapidly decreased ciliary beat frequency (CBF), as assessed by a photoelectric method, from 971 +/- 12 to 718 +/- 28 beats/min by 3 ppm SO2 and from 963 +/- 22 to 635 +/- 34 beats/min by 10 ppm SO2 (p < 0.001, in each case). This effect was reversed by washing out the SO2-containing medium and was accompanied by a corresponding decrease in intracellular levels of cyclic AMP. Preincubation of the epithelial cells with salbutamol, vasoactive intestinal peptide, prostaglandin E2 or 3-isobutyl-1-methylxanthine increased cyclic AMP levels and inhibited the decreases in both CBF and cyclic AMP in response to the subsequent application of SO2 at 3 ppm, whereas dexamethasone had no effect. These results suggest that SO2 decreases airway ciliary motility through the reduction of intracellular cyclic AMP concentration, and that drugs that increase endogeneous cyclic AMP may prevent the SO2-induced impairment of mucociliary transport in the respiratory tract.

Animals↗
PubMed1993

[Alveolar type II cells in centrilobular emphysema lesions of human lung--an ultrastructural study].

The lungs studied were surgically resected, mainly for lung cancer. All lungs had centrilobular emphysema. Emphysematous and non-emphysematous areas were identified by dissecting light microscopy. In emphysematous lesions, transmission electron microscopic observation revealed that (1) the shape of type II cells was associated with the changes of alveoli, such as type II cells were flattened in flattened alveolar wall; (2) the cells were cuboidal in the alveolar corner; (3) the number of close contacts between type II cells and interstitial cells was significantly decreased; (4) osmiophilic lamellated bodies in type II cells were normal in number and shape, and that type II cell hyperplasia was observed in the overlapping alveolar walls. These findings suggest that both injury and repair may occur in the alveolar epithelium of emphysematous lesions, and tissue repair may be impaired.

Humans↗
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↗