• We have studied the effect of neuropeptide Y on basal and vasoactive intestinal polypeptide–stimulated changes in the short-circuit current of strips of colonic mucosa from New Zealand white rabbits mounted in Ussing chambers. When administered to the basolateral surface, neuropeptide Y is found to decrease basal short-circuit current. Neuropeptide Y inhibits vasoactive intestinal peptide–stimulated increases in short-circuit current in a concentration-dependent fashion by a tetrodotoxin-insensitive mechanism. Also, neuropeptide Y inhibited increases in short-circuit current produced by direct stimulation of adenylate cyclase with forskolin. Furthermore, neuropeptide Y prevents vasoactive intestinal peptide–stimulated increases in tissue cyclic adenosine monophosphate levels. These results indicate that neuropeptide Y administered to the basolateral membrane inhibits vasoactive intestinal peptide–stimulated short-circuit current changes by a tetrodotoxin-insensitive mechanism that decreases tissue levels of cyclic adenosine 3′,5′-monophosphate.
(Arch Surg. 1990;125:1561 -1563)