Jun Tamaoki

Effects of New Quinolones on Transepithelial Electrical Potential Difference of Tracheal Mucosa In Vivo

ABSTRACT Superfusion of canine tracheal mucosa with 100 μg each of grepafloxacin and ciprofloxacin per ml reduced the electrical transepithelial potential difference in vivo by more than 50%. This effect was dose dependent, specific for new quinolones, and inhibited by Cl channel blockers, indicating that new quinolones attenuate Cl secretion across the airway epithelium.

Effect of histamine on airway transepithelial potential difference in vivo.

Histamine is one of the important mediators that causes a variety of allergic inflammatory responses in the airway. In the present study, to determine the effect of histamine on ion transport function across the airway mucosa, we measured transepithelial potential difference (PD) of rabbit tracheal mucosa under open-circuit conditionsin vivo. A high impedance voltmeter was used to measure PD between a fluid-filled and perfused recording bridge located on the airway surface and a reference bridge in the subcutaneous space. Addition of histamine to the perfusate produced a biphasic response of PD consisting of a rapid decrease within 15 sec and the subsequent plateau, which was followed by a sustained increase after 5 min of addition. Pretreatment of tracheal mucosa with the Na channel blocker amiloride greatly inhibited the early phase reduction of PD in response to histamine, but had no effect on the late phase elevation. On the other hand, pretreatment with the Cl channel blocker diphenylamine-2-carboxylate inhibited the late phase increase of PD completely.These results indicate that early and late responses of PD are dependent on Na and Cl, respectivly, and suggest that histamine may inhibit Na absorption and stimulate Cl secretion in the airway mucosa.

Prophylactic effect of azelasine on sulfur dioxide-induced inhibition of ciliary motility in airway epithelium.

We studied the effects of azelastine and salbutamol on the sulfur dioxide (SO2) -induced inhibition of airway ciliary motility. Azelastine and salbutamol dose-dependently increased ciliary beat frequency (CBF) of rabbit tracheal epithelium, as detrmined by a photoelectric technique. Perfusate bubbled with 10 ppm SO2 greatly decreased CBF and intracellular cyclic AMP levels, an effect that was reversed by pretreatment of cells with azelastine and salbntamol.Thus, azelastine might protect against SO2-induced airway injury by accumulating cyclic AMP in epithelial cells.