Mucosal histamine inhibits Na absorption and stimulates Cl secretion across equine tracheal epithelium

When the equine tracheal epithelium is mounted in Ussing chambers and bathed in plasma-like Ringer solution, the tissue generates a lumen-negative transepithelial potential (PD) of 22 mV and a short-circuit current (I(sc)) of 70-200 μA/cm². Mucosal addition of 10 μM histamine produces a transient increase in the I(sc) followed by a return to baseline or below. Mucosal addition of 2 μM diphenhydramine inhibits the I(sc) response to mucosal histamine, whereas 100 μM mucosal cimetidine produces no effect. The average initial increases in I(sc) over time for mucosal vs. serosal histamine addition are significantly different (17.32 ± 2.8 and 3.76 ± 0.69 μA/min, respectively). Pretreatment with mucosal amiloride significantly prolongs the effect of mucosal histamine on I(sc) over a 20-min period from 4.73 ± 0.33 to 15.48 ± 3.16 μA. When Cl is replaced by gluconate, mucosal histamine addition results in a gradual decrease in I(sc) and significantly reduces the effect of mucosal amiloride on I(sc) from 80.8% to 54.9%. Mucosal histamine inhibits the net transepithelial Na flux by 42% and stimulates the secretion of Cl by 106%. Subsequent addition of serosal bumetanide decreases net Cl secretion by 70%. These results suggest that histamine stimulates bumetanide-sensitive Cl secretion and inhibits amiloride-sensitive Na absorption; these effects are mediated by H₁ receptors at the apical membrane surface.