Regulation of amiloride-sensitive sodium absorption in murine airway epithelium by C-type natriuretic peptide.
We have previously shown that C-type natriuretic peptide (CNP), a guanylate cyclase agonist, can stimulate cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride secretion in murine airway epithelial cells via protein kinase (PK) A activation through the inhibition of cGMP-inhibited phosphodiesterases. In this paper, we show that CNP is also capable of reducing amiloride-sensitive sodium absorption in murine airway epithelium through a cGMP-dependent mechanism that is separate from the CFTR regulatory signaling pathway. Both murine tracheal and nasal tissues exhibit sensitivity to amiloride-sensitive sodium regulation by exogenously added CNP. CNP depolarized the nasal transepithelial potential difference by 6.3 +/- 0.5 mV, whereas the cGMP-inhibited phosphodiesterase inhibitor milrinone actually hyperpolarized the nasal transepithelial potential difference by 2.0 +/- 1.2 mV in mice homozygous for a CFTR stop mutation [CFTR(-/-)]. Inhibition of guanylate cyclase activity and PKG activity in normal mice resulted in an increase in amiloride-sensitive sodium absorption, suggesting that tonic regulation of amiloride-sensitive sodium absorption is in part due to basal cGMP levels and PKG activity.
Kelley
T J
TJ
Department of Pediatrics, Center for Human Genetics, Case Western Reserve University, Cleveland, Ohio 44106-4948, USA.
Cotton
C U
CU
Drumm
M L
ML
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000042:Absorption; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004848:Epithelium / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D020105:Milrinone; D009154:Mutation; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D020098:Natriuretic Peptide, C-Type; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
D010726:Phosphodiesterase Inhibitors; D011506:Proteins; D011728:Pyridones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D020098:Natriuretic Peptide, C-Type; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000584:Amiloride; D012964:Sodium; D017868:Cyclic AMP-Dependent Protein Kinases; D006152:Cyclic GMP; D020105:Milrinone