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Biomedical subjects

J Tamaoki

Publications and source records attributed to J Tamaoki.

At least 163 records · Page 9Linked to original sources
PubMed1991

Ambroxol inhibits Na+ absorption by canine airway epithelial cells in culture.

To study the effect of ambroxol on ion transport functions of airway mucosa, we measured bioelectric properties of canine cultured tracheal epithelium under short-circuit conditions in-vitro. Addition of ambroxol to the submucosal but not to the mucosal solution in an Ussing chamber decreased short-circuit current, transepithelial potential difference and cell conductance. The ambroxol-induced decrease in short-circuit current was not affected by bumetanide or diphenylamine-2-carboxylate, but it was abolished by pretreatment of cells with amiloride. These results suggest that ambroxol may selectively inhibit Na+ absorption by airway epithelium, thereby increasing water composition in airway surface fluid and reducing mucus viscosity.

Absorption↗
PubMed1991

Lipopolysaccharide from Klebsiella pneumoniae inhibits Na+ absorption in canine tracheal epithelium.

The effect of lipopolysaccharide (LPS) from Klebsiella pneumoniae on the bioelectric properties of canine cultured tracheal epithelium was examined. LPS decreased short-circuit current (Isc), and its effects on Isc were reduced when Isc was inhibited by amiloride and indomethacin. We speculate that LPS may selectively inhibit Na+ absorption through the inhibition of prostaglandin synthesis by airway epithelium.

Absorption↗
PubMed1991

Atrial natriuretic factor inhibits ciliary motility in cultured rabbit tracheal epithelium.

To study the effect of atrial natriuretic factor (ANF) on airway ciliary motility, we measured ciliary beat frequency by a photoelectric method in response to ANF in cultured tracheal epithelial cells from rabbits. Addition of ANF but not [Tyr8]ANF-(5-27) decreased ciliary beat frequency in a dose-dependent fashion; the maximal decrease from the baseline value was 24.1 +/- 1.5% (+/- SE, P less than 0.001), and a half-maximal inhibitory concentration (IC50) was 3 x 10(-12) M. Inhibition of neutral endopeptidase activity by phosphoramidon (10(-6) M) or thiorphan (10(-6) M) potentiated the effect of ANF so that the dose-response curve for ANF was shifted to lower concentrations by approximately 0.5 log units (P less than 0.05, in each case). The inhibition of ciliary motility induced by ANF was not affected by the blockade of arachidonic acid metabolism with indomethacin, piroxicam, or nordihydroguaiaretic acid, but it was blocked by methylene blue, a soluble guanylate cyclase inhibitor, and was potentiated by M & B 22948, a guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor. The intracellular cGMP levels were increased by ANF, an effect that was further potentiated by phosphoramidon or thiorphan. These results suggest that ANF inhibits ciliary motility presumably through a guanylate cyclase-dependent regulatory pathway and that neutral endopeptidase may play a role in modulating the ANF effect on airway mucociliary transport function.

Animals↗
PubMed1991

Effect of neutral endopeptidase inhibition on substance-P-induced increase in short-circuit current of canine cultured tracheal epithelium.

We studied the effect of substance P (SP) on the electric properties of cultured canine tracheal epithelium and its possible modulation by neutral endopeptidase (NEP) by Ussing's short-circuited technique in vitro. Addition of SP (5 x 10(-6) M) to the mucosal side increased short-circuit current (SCC) from 5.1 +/- 0.9 to 10.3 +/- 2.2 microA/cm2 (mean +/- SE; p less than 0.01), which was accompanied by increases in transepithelial potential difference and conductance. The effect of the mucosal SP on SCC was dose-dependent, with the maximal increase from the baseline value being 5.8 +/- 1.0 microA/cm2 observed at 5 x 10(-5) M. The NEP inhibitor phosphoramidon (10(-5) M) did not affect these responses. On the other hand, SCC was not altered by the addition of SP to the submucosal side. However, it was increased dose-dependently in the presence of phosphoramidon (10(-5) M) but not in the presence of captopril, bestatin or leupeptin. This stimulatory effect of submucosal SP was abolished by furosemide, diphenylamine-2-carboxylate and Cl-free medium, but not by amiloride. These results suggest that SP may selectively stimulate Cl secretion across the airway epithelium and that this effect may be modulated by submucosal NEP.

Amiloride↗
PubMed1991

Endothelin stimulates ciliary beat frequency and chloride secretion in canine cultured tracheal epithelium.

Endothelin, an endothelium-derived vasoconstrictor peptide, has recently been reported to exist in airway epithelial cells. To elucidate a possible role of endothelin on epithelial functions, we studied the effects of this peptide on ciliary beat frequency (CBF) and electrical properties of canine cultured tracheal epithelium by a microphoto-oscillation method and Ussing's short-circuited technique, respectively. Endothelin dose-dependently increased CBF, the maximal increase above the baseline value and EC50 being 32.3 +/- 4.0% (P less than 0.001) and 3 nM, respectively. This effect was moderately attenuated by pretreatment of cells with indomethacin and greatly reduced by Ca2(+)-free medium. Addition of endothelin (10(-6) M) to the mucosal bath of Ussing chamber increased short-circuit current from 5.1 +/- 1.2 to 9.4 +/- 1.7 microA/cm2 (P less than 0.05) and potential difference from 2.9 +/- 0.4 to 5.0 +/- 0.9 mV (P less than 0.05), an effect that was inhibited by indomethacin or Ca2(+)-deficiency and was abolished by the Cl transport inhibitor bumetanide or substitution of Cl with iodide in the medium. These results indicate that endothelin stimulates ciliary motility and Cl secretion probably through an increase in cytosolic Ca2+ and partially a prostaglandin synthesis in canine tracheal epithelium, and suggest that this peptide might play a role in modulating airway mucociliary transport functions.

Animals↗
PubMed1991

[Effect of roxithromycin on ciliary motility of rabbit tracheal epithelium in culture].

Mucociliary transport plays an important role in the lung defense mechanism by clearing inhaled particles and bacteria from the respiratory tract. In the present study, we tried to determine whether roxithromycin (RXM), a new semisynthetic macrolide, can affect airway mucociliary functions and, if so, what the mechanism of its action is. To do so we measured ciliary beat frequency (CBF) of rabbit cultured tracheal epithelium by a photoelectric method. Addition of RXM (10(-4) M) to a Rose chamber containing epithelial cells caused a rapid increase in CBF from 12.1 +/- 0.6 to 16.2 +/- 0.8 Hz (mean +/- SE, p less than 0.001) within 5 min. This effect was dose-dependent, the maximal increase from the baseline CBF and EC50 being 34.6 +/- 5.0% and 3 x 10(-6)M, respectively. The increase in CBF produced by RXM (3 x 10(-6)M) was not influenced by pretreatment of cells with the beta-adrenergic blocker propranolol, the lipoxygenase inhibitor AA-861, or the Ca(2+)-channel blocker verapamil, but it was partially reduced by the cyclooxygenase inhibitor indomethacin (p less than 0.05). Intracellular cyclic AMP levels were increased by 10(-4)M RXM from 42.3 +/- 8.7 to 72.7 +/- 7.0 pmoles/mg protein (p less than 0.05). These results indicate that RXM stimulates ciliary motility; an effect that may be attributed at least in part to the synthesis of cyclooxygenase products and cyclic AMP, and suggest that this macrolide could be useful in treating patients with impaired mucociliary transport in the airway.

Animals↗
PubMed1991

[Effect of histamine on electrical properties of airway epithelium and its antagonism by azelastine].

To elucidate the mechanism of the action of histamine on bioelectric properties of the airway epithelium and the fact that the anti-allergic agent azelastine is possibly antagonistic to it, we studied canine cultured tracheal epithelium under short-circuit conditions in vitro. Addition of histamine to the submucosal but not mucosal bath of Ussing chamber increased short-circuit current (Isc) in a dose-dependent fashion, the maximal increase and the EC50 value being 5.7 +/- 0.9 microA/cm2 (mean +/- SE, p less than 0.001) and 3 x 10(-6) M, respectively. Pretreatment of tissues with pyrilamine abolished the histamine-induced increase in Isc (p less than 0.001), whereas cimetidine had no effect. In addition, the histamine action on Isc was effectively depressed by the Cl channel blocker diphenylamine-2-carboxylate, Cl-free medium, and indomethacin. The release of PGE2 and PGF2 alpha was significantly enhanced by the submucosal application of histamine. Pretreatment of tissues with azelastine dose-dependently attenuated the increase in Isc induced by 10(-4) M histamine. These results indicate that histamine increases the airway epithelial Isc via stimulation of prostaglandin synthesis and subsequent movement of Cl toward the lumen, and that azelastine may be useful in preventing histamine-induced water secretion in the airway.

Animals↗
PubMed1991

[Effect of histamine on electrical properties in canine tracheal epithelium].

To characterize the action of histamine on ion transport across the airway mucosa, we measured the electrical properties of cultured tracheal epithelium from dogs by Ussing's short-circuited technique in vitro. The addition of histamine to the submucosal side increased short-circuit current (Isc), whereas mucosal addition of histamine had no effect. The histamine-induced increase in Isc was dose-dependent with the maximal increase from the baseline value and EC50 being 4.4 +/- 0.5 microA/cm2 and 10(-6) M, respectively. We also tested the effects of pharmacological blocking agents on the histamine-induced Isc increase. The effect of histamine on Isc was partially inhibited by pretreatment of cells with amiloride, furosemide and diphenylamine carboxylate. Furthermore, the effect of histamine was inhibited by pyrilamine, but not by cimetidine. To determine the contributions of several intracellular second messenger systems to the histamine-induced increase in Isc, we studied the change of Isc by pretreatment of cells with indomethacin, mepacrine and H-7. The increase in Isc produced by histamine was inhibited by indomethacin and mepacrine but not H-7. These results suggest that histamine stimulates both Cl secretion and Na absorption and may affect the subsequent movement of water across the airway epithelium through the activation of submucosal H1-receptor probably involving prostaglandin synthesis.

Animals↗
PubMed1990

Inhibition by loperamide of chloride transport across canine cultured tracheal epithelium.

We studied the effect of loperamide on electrical properties of canine cultured tracheal epithelium by Ussing's short-circuited technique. Addition of loperamide to the mucosal bath decreased the short-circuit current, transepithelial potential difference and conductance, whereas submucosal loperamide had no effect. This inhibitory effect was attenuated by furosemide, diphenylamine-2-carboxylate and Cl(-)-free medium but not by amiloride or naloxone. Thus, loperamide may selectively inhibit Cl- secretion across airway epithelium through a non-opiate-dependent mechanism.

Amiloride↗
PubMed1990

Effects of beta-endorphin and dynorphin A on cholinergic neurotransmission in canine airway smooth muscle.

To determine the effects of the opioid peptides, beta-endorphin and dynorphin A, on airway smooth muscle function and its possible modulation by tissue peptidases, we studied canine bronchial segments under isometric conditions in vitro. Addition of beta-endorphin or dynorphin A did not alter the resting tension. However, beta-endorphin (10(-6) M) but not dynorphin A decreased the contractile responses to electrical field stimulation (EFS, 0.5-40 Hz). This effect was dose-dependent and reversed by naloxone. In contrast, acetylcholine-induced contractions were not affected by these opioids. The beta-endorphin-induced inhibition of the contractile responses to EFS was not augmented by peptidase inhibitors such as thiorphan, captopril, bestatin and leupeptin. These results suggest that beta-endorphin prejunctionally inhibits parasympathetic muscle contraction, and that endogenous peptidases do not play a modulatory role in this effect of beta-endorphin.

Animals↗
PubMed1990

Calcitonin gene-related peptide augments parasympathetic contraction of rabbit tracheal smooth muscle in vitro.

The effect of calcitonin gene-related peptide (CGRP) on parasympathetic contraction of rabbit airway smooth muscle was studied under isometric conditions in vitro. CGRP (10(-7) M) did not contract tracheal smooth muscle, but it potentiated the contractile response to electrical field stimulation (EFS) in a dose-dependent manner, the maximal increase from the baseline response being 14.4 +/- 6.2%. In contrast, the contractile responses to exogenously administered acetylcholine were not altered by this peptide. The CGRP-induced potentiation of the contractile responses to EFS was further augmented by physostigmine (123.1%), but not influenced by phentolamine, propranolol, indomethacin, or thiorphan, an enkephalinase inhibitor. These results suggest that CGRP augments the neurally mediated contraction of rabbit airway smooth muscle probably through a prejunctional mechanism and that this effect may not be modulated by tissue enkephalinase.

Acetylcholine↗
PubMed1990

Angiotensin II stimulates airway ciliary motility in rabbit cultured tracheal epithelium.

We studied the effect of angiotensin II on ciliary activity in cultured rabbit tracheal epithelium in vitro. Administration of angiotensin II (10(-6) M) elicited an increase in ciliary beat frequency (CBF), as assessed by a photoelectric method, from the baseline value of 906 +/- 21 to 1260 +/- 33 beats min-1 (mean +/- SE, P less than 0.001). This ciliostimulatory effect was dose-dependent, with the maximal increase and EC50 value being 35.6 +/- 5.2% (P less than 0.001) and 5 x 10(-12) M respectively. Nifedipine, Ca2(+)-free medium, indomethacin and the phospholipase A2 inhibitor mepacrine, but not nordihydroguaiaretic acid, reduced the change in CBF. The ciliostimulation induced by angiotensin II was abolished by pretreatment of tissues with [Sar1-Ile8]angiotensin II, an angiotensin II receptor antagonist. Angiotensin II did not increase cyclic AMP levels in epithelial cells. These results suggest that angiotensin II interacts with its specific receptors and stimulates airway ciliary activity through a Ca2(+)-dependent prostaglandin release, without affecting intracellular cyclic AMP levels. Thus, angiotensin II may modulate mucociliary transport function in the respiratory tract.

Angiotensin II↗
PubMed1990

Relaxation of canine airway smooth muscle by the heparin preservative benzyl alcohol.

To characterize the actions of heparin and its common preservative benzyl alcohol (BA) on airway smooth muscle functions, we studied the effects of purified heparin, commercial heparin salt solution (HSS) containing heparin and BA, and BA on the contractile responses of canine bronchial segments to various agonists under isometric conditions in vitro. Addition of HSS or the equivalent volume of BA reversibly depressed acetylcholine-induced contraction in a dose-dependent fashion, IC50 values being 5.7 +/- 1.1 (SE) mM of BA, whereas purified heparin had no effect. This depression was not affected by pretreatment of tissues with propranolol, indomethacin or ouabain, or removal of epithelium, and BA at sufficient concentrations to cause muscle relaxation did not alter intracellular adenosine 3',5'-cyclic monophosphate contents. BA also attenuated the contractile responses to electrical field stimulation, histamine, and serotonin, but it was without effect on those to KCl. In addition, the acetylcholine-induced enhancement of hydrolysis of phosphatidylinositol 4,5-biphosphate in the lipid fraction and the resultant production of phosphatidic acid were inhibited in the presence of BA. These results suggest that the heparin preservative BA but not heparin relaxes airway smooth muscle, probably through the decrease in intracellular Ca2+ release by inhibiting agonist-mediated phosphatidylinositol turnover.

Acetylcholine↗
PubMed1990

Effects of lipopolysaccharide from Pseudomonas aeruginosa on airway smooth muscle functions in guinea pigs.

To elucidate the mechanisms of airway hyperreactivity induced by lipopolysaccharide (LPS), we studied isolated tracheal segments from guinea pigs under isometric conditions in vitro. Guinea pigs were injected intraperitoneally with endotoxin (1 mg/kg; LPS from Pseudomonas aeruginosa, serotype 10) for 4 days, and animals treated with sterile nonpyrogenic saline served as controls. Histological examination of trachea revealed moderate structural damage of epithelial layer in the LPS-treated group. Treatment with LPS potentiated the contractile responses of tracheal smooth muscle to acetylcholine, causing a leftward displacement of dose-response curves so that the EC50 values decreased from 1.1 +/- 3.7 x 10(-5) to 4.4 +/- 3.7 x 10(-7) M (mean +/- SE, p less than 0.01). Likewise, LPS shifted the dose-response curves for histamine and substance P to lower concentrations by approximately 0.5-1.0 log U. Each of these potentiations was not affected by pretreatment of tissues with indomethacin or propranolol. Addition of isoproterenol to tracheal segments precontracted with acetylcholine caused concentration-dependent relaxation, an effect that was significantly greater in controls than in the LPS-treated group. These results suggest that airway hyperreactivity induced by LPS in guinea pigs may be attributed to a decreased ability of respiratory epithelial cells to generate a relaxing factor.

Animals↗
PubMed1990

Neutral endopeptidase inhibitor potentiates the tachykinin-induced increase in ciliary beat frequency in rabbit trachea.

We used cultured rabbit tracheal epithelium to determine the effect of mammalian-derived tachykinin on airway ciliary activity and its modulation by neutral endopeptidase EC 3.4.24.11 (NEP). Neurokinin A (NKA) caused dose-dependent increases in ciliary beat frequency (CBF), as measured by a photoelectric method, with the maximal increase from the baseline 15.7 +/- 1.7% (mean +/- SEM, p less than 0.01), whereas substance P (SP) had no effect. The NKA-induced increase in CBF was not inhibited by phentolamine, propranolol, or atropine, but it was abolished by the tachykinin antagonist [D-Pro2, D-Trp7,9]SP. Pretreatment of tissue with thiorphan (10(-5) M), a NEP inhibitor, had little effect on CBF responses to NKA; however, it significantly potentiated the responses to SP (14.9 +/- 3.0%, p less than 0.01). Other peptidase inhibitors, including captopril, bestatin, and leupeptin, did not alter the tachykinin-induced CBF response, suggesting that angiotensin converting enzyme, aminopeptidases, and serine proteinases do not modulate ciliary activity in response to tachykinins. These results suggest that NKA increases CBF by acting directly on tachykinin receptors and that NEP may play a role in modulating the tachykinin-induced stimulatory effects on CBF.

Animals↗
PubMed1990

Effect of the anti-asthmatic agent KC-404 on the contractile responses of rabbit airway smooth muscle to tachykinins.

To characterize the antagonistic action of KC-404, an anti-asthmatic agent, against the tachykinin-mediated bronchoconstriction, we studied the effect of this drug on the contractile responses of rabbit tracheal smooth muscle to neurokinin A (NKA) and substance P (SP) under isometric conditions in vitro. Addition of KC-404 relaxed the tracheal rings precontracted with NKA and SP in a dose-dependent fashion but had only a small effect on the contractile responses to acetylcholine and histamine. This inhibitory action of KC-404 was likewise noted even in the presence of atropine. In addition, each of NKA and SP at a concentration insufficient to alter the resting tone enhanced the contractile response to electrical filed stimulation, an effect that was dose-dependently attenuated by the subsequent application of KC-404. These results suggest that KC-404 may antagonize the bronchoconstrictor actions of tachykinins by interacting with their specific receptors on smooth muscle cells as well as on cholinergic nerve terminals in the airway.

Animals↗
PubMed1990

[Indomethacin inhalation therapy].

We studied the effect indomethacin (IND) on electrical properties of airway epithelial cells and on sputum production in patients with chronic respiratory infection. Addition of IND (3 x 10(-6) M) to the mucosal side of Ussing chamber reduced short-circuit current from 5.9 +/- 1.2 to 1.7 +/- 0.5 microA/cm2 (p less than 0.001, n = 12) in canine cultured tracheal epithelium, an effect that was dependent on CI. Inhalation of IND for two weeks resulted in a decrease in the amount of sputum from 208 +/- 25 to 102 +/- 19 ml/day, (p less than 0.01, n = 13), and the concentrations of cyclooxygenase products in the sputum without alteration of inflammatory parameters. These results indicate that IND inhalation is a promising therapy in improving excessive sputum production and that this effect may be attributable to inhibition of Cl secretion and the subsequent reduction in water movement toward the airway lumen.

Administration, Inhalation↗