Neuropeptide Y inhibits ciliary beat frequency in human ciliated cells via nPKC, independently of PKA

• Published in: American Journal of Physiology: Cell Physiology Vol. 275; no. 2; pp. C440 - C448
• Main Authors: Wong, Lid B, Park, C. Lucy, Yeates, Donovan B
• Format: Journal Article
• Language: English
• Published: United States 01.08.1998
• Subjects: Adenylyl Cyclases - metabolism; Adolescent; Adult; Bronchi - cytology; Bronchi - physiology; Calcium-Transporting ATPases - metabolism; Carbazoles - pharmacology; Cilia - drug effects; Cilia - physiology; Colforsin - pharmacology; Enzyme Inhibitors - pharmacology; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - physiology; Humans; Indoles - pharmacology; Isoenzymes - metabolism; Kinetics; Lasers; Maleimides - pharmacology; Middle Aged; Naphthalenes - pharmacology; Neuropeptide Y - pharmacology; Neuropeptide Y - physiology; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Scattering, Radiation; Time Factors; Trachea - cytology; Trachea - physiology
• ISSN: 0363-6143; 0002-9513; 1522-1563
• DOI: 10.1152/ajpcell.1998.275.2.c440

Departments of Medicine, Pediatrics, and Bioengineering, University of Illinois at Chicago and Veterans Affairs Chicago Health Care System, Chicago, Illinois 60612 The intracellular mechanisms whereby the inhibitory neurotransmitter neuropeptide Y (NPY) decreases ciliary beat frequency (CBF) were investigated in cultured human tracheal and bronchial ciliated cells. CBF was measured by nonstationary analysis laser light scattering. NPY at 1 and 10 µM decreased CBF from a baseline of 6.7 ± 0.5 ( n  = 12) to 6.1 ± 0.5 ( P  < 0.05) and 5.8 ± 0.4 ( P < 0.01) Hz, respectively. Prior application of PYX-1, an NPY antagonist, prevented the decreases of CBF induced by both doses of NPY. Two broad protein kinase C (PKC) kinase inhibitors, staurosporine and calphostin C, also abolished the NPY-induced decrease in CBF. The NPY-induced decrease in CBF was abolished by GF 109203X, a novel PKC (nPKC) isoform inhibitor, whereas this decrease in CBF was not attenuated by Gö-6976, a specific inhibitor of conventional PKC isoforms. Because pretreatment with NPY did not block the stimulation of CBF by forskolin and pretreatment with forskolin did not abolish the NPY-induced inhibition of CBF, this NPY receptor-mediated signal transduction mechanism appears to be independent of the adenylate cyclase-protein kinase A (PKA) pathway. Inhibition of Ca 2+ -ATPase by thapsigargin also prevented the suppression of CBF induced by subsequent application of NPY. These novel data indicate that, in cultured human epithelia, NPY decreases CBF below its basal level via the activation of an nPKC isoform and Ca 2+ -ATPase, independent of the activity of PKA. This is consistent with the proposition that NPY is an autonomic efferent inhibitory neurotransmitter regulating mucociliary transport. Gö-6976; GF 109203X; neuropeptide Y receptor subtype 1 (Y 1 ); neuropeptide Y receptor subtype 2 (Y 2 ); thapsigargin