Peptides increase anion conductance of canine trachea: an effect on tight junctions

The ionic basis for the rapid reduction in potential difference (dip) produced on luminal addition of substance P and related peptides was analysed by altering the electromotive force and chemical gradients across the isolated, canine tracheal epithelium. The dip could be exaggerated, minimised or reversed by increasing, decreasing or reversing the basal potential difference, and the intercept of the line relating the two was close to zero when the Cl- compositions of the two bathing solutions were identical. Luminal Cl- replacement by a non-permeant anion (isethionate) attenuated the dip which was, however, exaggerated by a permeant anion (nitrate). Replacement of serosal Na+ or luminal HCO3- had no significant effect on the magnitude of the dip. The tachykinins exhibited cross-tachyphylaxis with each other, indicating a common receptor. Bradykinin, a structurally unrelated peptide, also produced dips upon luminal addition, but showed no cross-tachyphylaxis with the tachykinins. Again, a linear relation between basal potential difference and the dip elicited by bradykinin was observed. Based on current awareness of the bioelectric properties of the canine tracheal epithelium, we suggest that these peptides modulate paracellular anion permeabilities.