Simultaneous measurement of mechanical responses and transepithelial potential difference and resistance, in guinea-pig isolated, perfused trachea using a novel apparatus: Pharmacological characterization

Jing, Y. P.; Dowdy, Janet A.; Scott, Michael R. Van; Fedan, Jeffrey S.

doi:10.1016/j.ejphar.2008.09.009

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…It allows assessment of the role of the epithelium in integrated responses of the organ (Jing et al, 2008b) and has been used to demonstrate that both the apical and basolateral membranes of airway epithelial cells respond to hyperosmolar challenge (Fedan et al, 2004a). After sacrifice, a 4.2 cm-section of trachea was excised, cleaned in gassed MKH solution, and mounted on a perfusion holder.…”

Section: Methodsmentioning

confidence: 99%

“…Functional evidence was obtained to suggest that the EpDRF release initiated by hyperosmolar challenge is unrelated to cell shrinkage; this evidence was indirect. Hyperosmolar challenge evokes electrophysiological responses that are complex, osmolyte-specific and concentration-dependent, polarized across the epithelium and involve activation of JNK, PKC and phosphatases (Wu et al, 2004; Jing et al, 2008b). The osmosensor which triggers these responses is undescribed.…”

Section: Introductionmentioning

confidence: 99%

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Tracheal epithelium cell volume responses to hyperosmolar, isosmolar and hypoosmolar solutions: relation to epithelium-derived relaxing factor (EpDRF) effects

Fedan¹,

Thompson²,

Ismailoglu³

et al. 2013

Front. Physiol.

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In asthmatic patients, inhalation of hyperosmolar saline or D-mannitol (D-M) elicits bronchoconstriction, but in healthy subjects exercise causes bronchodilation. Hyperventilation causes drying of airway surface liquid (ASL) and increases its osmolarity. Hyperosmolar challenge of airway epithelium releases epithelium-derived relaxing factor (EpDRF), which relaxes the airway smooth muscle. This pathway could be involved in exercise-induced bronchodilation. Little is known of ASL hyperosmolarity effects on epithelial function. We investigated the effects of osmolar challenge maneuvers on dispersed and adherent guinea-pig tracheal epithelial cells to examine the hypothesis that EpDRF-mediated relaxation is associated with epithelial cell shrinkage. Enzymatically-dispersed cells shrank when challenged with ≥10 mOsM added D-M, urea or NaCl with a concentration-dependence that mimics relaxation of the of isolated perfused tracheas (IPT). Cells shrank when incubated in isosmolar N-methyl-D-glucamine (NMDG) chloride, Na gluconate (Glu), NMDG-Glu, K-Glu and K2SO4, and swelled in isosmolar KBr and KCl. However, isosmolar challenge is not a strong stimulus of relaxation in IPTs. In previous studies amiloride and 4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid (DIDS) inhibited relaxation of IPT to hyperosmolar challenge, but had little effect on shrinkage of dispersed cells. Confocal microscopy in tracheal segments showed that adherent epithelium is refractory to low hyperosmolar concentrations that induce dispersed cell shrinkage and relaxation of IPT. Except for gadolinium and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), actin and microtubule inhibitors and membrane permeabilizing agents did not affect on ion transport by adherent epithelium or shrinkage responses of dispersed cells. Our studies dissociate relaxation of IPT from cell shrinkage after hyperosmolar challenge of airway epithelium.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tracheal epithelium cell volume responses to hyperosmolar, isosmolar and hypoosmolar solutions: relation to epithelium-derived relaxing factor (EpDRF) effects

Fedan¹,

Thompson²,

Ismailoglu³

et al. 2013

Front. Physiol.

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Insights on the role of boron containing moieties in the design of new potent and efficient agonists targeting the β2 adrenoceptor

Soriano-Ursúa

Arias‐Montaño²,

Correa‐Basurto

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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Airway epithelium-derived relaxing factor: myth, reality, or naivety?

Vanhoutte

2013

American Journal of Physiology-Cell Physiology

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The presence of a healthy epithelium can moderate the contraction of the underlying airway smooth muscle. This is, in part, because epithelial cells generate inhibitory messages, whether diffusible substances, electrophysiological signals, or both. The epithelium-dependent inhibitory effect can be tonic (basal), synergistic, or evoked. Rather than a unique epithelium-derived relaxing factor (EpDRF), several known endogenous bronchoactive mediators, including nitric oxide and prostaglandin E 2, contribute. The early concept that EpDRF diffuses all the way through the subepithelial layers to directly relax the airway smooth muscle appears unlikely. It is more plausible that the epithelial cells release true messenger molecules, which alter the production of endogenous substances (nitric oxide and/or metabolites of arachidonic acid) by the subepithelial layers. These substances then diffuse to the airway smooth muscle cells, conveying epithelium dependency.

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Simultaneous measurement of mechanical responses and transepithelial potential difference and resistance, in guinea-pig isolated, perfused trachea using a novel apparatus: Pharmacological characterization

Cited by 3 publications

References 24 publications

Tracheal epithelium cell volume responses to hyperosmolar, isosmolar and hypoosmolar solutions: relation to epithelium-derived relaxing factor (EpDRF) effects

Tracheal epithelium cell volume responses to hyperosmolar, isosmolar and hypoosmolar solutions: relation to epithelium-derived relaxing factor (EpDRF) effects

Insights on the role of boron containing moieties in the design of new potent and efficient agonists targeting the β2 adrenoceptor

Airway epithelium-derived relaxing factor: myth, reality, or naivety?

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