Neuropeptide Y inhibits the protein kinase C-stimulated Cl(-) secretion in the human colonic cell line HT29cl.19A cell line via multiple sites
Autor: | Jack A. Groot, Judith C. J. Oprins, Hetty Bouritius, R. B. Bajnath |
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Přispěvatelé: | Cognitive and Systems Neuroscience (SILS, FNWI) |
Rok vydání: | 2001 |
Předmět: |
medicine.medical_specialty
Biology Calcium in biology Membrane Potentials chemistry.chemical_compound Chlorides Internal medicine medicine Cyclic AMP Humans Secretion Neuropeptide Y Protein kinase C Phorbol 12 13-Dibutyrate Protein Kinase C Epithelial polarity Pharmacology Forskolin Ionomycin Colforsin Electric Conductivity Apical membrane Neuropeptide Y receptor Cell biology Endocrinology chemistry Colonic Neoplasms Potassium Calcium HT29 Cells |
Zdroj: | European Journal of Pharmacology, 416(1-2), 43-50. Elsevier |
ISSN: | 0014-2999 |
DOI: | 10.1016/S0014-2999(01)00869-X |
Popis: | Neuropeptide Y is known to exert inhibitory effects on ion secretion in the intestine by reducing the activity of adenylyl cyclase. In the human intestinal epithelial cell line HT29cl.19A, it has been previously shown that neuropeptide Y inhibits the electrophysiological phenomena related to Cl− secretion, when induced by elevation of cAMP via forskolin. Moreover, the secretion induced via elevation of intracellular calcium levels via muscarinic activation can be inhibited by neuropeptide Y. Part of these inhibitions appeared to be due to lowered calcium activity in the epithelial cells, thereby reducing the basolateral K+ conductance. The phorbol ester 4-phorbol-12,13-dibutyrate (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 that neuropeptide Y inhibits the PDB-induced secretion at two sides: one located 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 direct effect of neuropeptide Y on the K+ conductance. This was concluded from the observation that neuropeptide Y could also reduce basolateral K+ conductance when intracellular calcium was dramatically increased by ionomycin. The observed inhibitory effects suggest that neuropeptide Y is a very powerful antisecretory peptide in human intestinal epithelial cells. |
Databáze: | OpenAIRE |
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