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-mu-A/cm2. Mucosal addition of 10-mu-M histamine produces a transient increase in the I(sc) followed by a return to baseline or below. Mucosal addition of 2-mu-M diphenhydramine inhibits the I(sc) response to mucosal histamine, whereas 100-mu-M 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-mu-A/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-mu-A. 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 H-1 receptors at the apical membrane surface.