The effect of peptide YY (PYY) on active electrolyte transport in rat
colon was studied under short-circuited conditions. PYY (10(-6) M) dec
reased the basal short-circuit current (I-sc) in both the distal and p
roximal segments of the colon. The decrease in I-sc induced by PYY in
the distal colon was about 3 times larger than that in the proximal co
lon. The response to PYY was inhibited by diphenylamine 2-carboxylate,
a specific blocker of the Cl-channel, but not by amiloride, a Na-chan
nel blocker. Unidirectional flux measurements in the distal colon reve
aled that PYY increased the net Na and Cl absorption and decreased the
serosal-to-mucosal Cl flux. PYY inhibited the neurally mediated secre
tory response to electrical field stimulation in a concentration-depen
dent manner. PYY was also shown to reduce the direct action of the cho
linergic agonist bethanechol on the epithelium. These results suggest
that PYY inhibits electrogenic Cl secretion and stimulates electroneut
ral NaCl absorption via both presynaptic and postsynaptic sites in the
distal colon.