NEUROPEPTIDE-Y INHIBITS ION SECRETION IN INTESTINAL EPITHELIUM BY REDUCING CHLORIDE AND POTASSIUM CONDUCTANCE

Neuropeptide Y (NPY) is probably the most abundant neuropeptide, with a plethora of central as well. as peripheral effects, including its pr oabsorptive action in the gastro-intestinal tract. The effects of NPY on electrical parameters related to three different pathways stimulati ng ion secretion were investigated using the human intestinal cell lin e HT29c1.19A. Transepithelial potential and resistance were measured w ith the preparation maintained in a horizontal Ussing chamber, allowin g simultaneous measurement of the membrane potential and determination of the fractional resistance of the apical cell membrane. It was foun d that application of NPY, after the adenylyl-cyclase-activating drug forskolin, resulted in complete inhibition of forskolin-induced effect s within approximately 20 min. The secretion stimulated by adenosine a ppeared to be insensitive to NPY. The acetylcholine analogue carbachol stimulates ion secretion by increasing intracellular free calcium con centrations ([Ca2+](i)) which activates the basolateral potassium (K+) conductance. NPY caused 50% inhibition of the effect of carbachol. Me asurements of [Ca2+](i) showed that NPY inhibited the carbachol-induce d rise in [Ca2+](i), which correlates with the reduced activation of b asolateral K+ channels. From this study we conclude that NPY inhibits cAMP-stimulated as well as Ca2+-stimulated secretion via a reduction i n the apical Cl- and basolateral K+ conductance. This double effect ma kes NPY an effective proabsorptive peptide.