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 proabsorptive action in the gastro-intestinal tract. The effects of NPY on electrical parameters related to three different pathways stimulating ion secretion were investigated using the human intestinal cell line HT29cl.19A. Transepithelial potential and resistance were measured with the preparation maintained in a horizontal Ussing chamber, allowing simultaneous measurement of the membrane potential and determination of the fractional resistance of the apical cell membrane. It was found that application of NPY, after the adenylyl-cyclase-activating drug forskolin, resulted in complete inhibition of forskolin-induced effects within approximately 20 min. The secretion stimulated by adenosine appeared to be insensitive to NPY. The acetylcholine analogue carbachol stimulates ion secretion by increasing intracellular free calcium concentrations ([Ca2+]i) which activates the basolateral potassium (K+) conductance. NPY caused 50% inhibition of the effect of carbachol. Measurements of [Ca2+]i showed that NPY inhibited the carbachol-induced rise in [Ca2+]i, which correlates with the reduced activation of basolateral K+ channels. From this study we conclude that NPY inhibits cAMP-stimulated as well as Ca2+-stimulated secretion via a reduction in the apical Cl- and basolateral K+ conductance. This double effect makes NPY an effective proabsorptive peptide.