Neuropeptide Y inhibits the protein kinase C-stimulated Cl- secretion in the human colonic cell line HT29c1.19A cell line via multiple sites

Neuropeptide Y is known to exert inhibitory effects on ion secretion in the intestine by reducing the activity of adenylyl cyclase. In the human intes tinal epithelial cell line HT29cl.19A, it has been previously shown that ne uropeptide Y inhibits the electrophysiological phenomena related to Cl- sec retion, when induced by elevation of cAMP via forskolin. Moreover, the secr etion induced via elevation of intracellular calcium levels via muscarinic activation can be inhibited by neuropeptide Y. Part of these inhibitions ap peared to be due to lowered calcium activity in the epithelial cells, there by reducing the basolateral K+ conductance. The phorbol ester 4-phorbol-12, 13-di-butyrate (PDB) can induce secretion in this cell line via activation of protein kinase C as well; however, the effect of neuropeptide Y on this pathway has not yet been studied. In the present experiments, it is shown t hat neuropeptide Y inhibits the PDB-induced secretion at two sides: one loc ated in the apical membrane and another in the basolateral membrane. It is shown that the latter effect can, at least partially, be explained via a di rect effect of neuropeptide Y on the K+ conductance. This was concluded fro m the observation that neuropeptide Y could also reduce basolateral K+ cond uctance when intracellular calcium was dramatically increased by ionomycin. The observed inhibitory effects suggest that neuropeptide Y is a very powe rful antisecretory peptide in human intestinal epithelial cells. (C) 2001 E lsevier Science B.V. All rights reserved.