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 guan ylate cyclase agonist, can stimulate cystic fibrosis transmembrane con ductance regulator (CFTR)-mediated chloride secretion in murine airway epithelial cells via protein kinase (PK) A activation through the inh ibition of cGMP-inhibited phosphodiesterases. In this paper, we show t hat CNP is also capable of reducing amiloride-sensitive sodium absorpt ion in murine airway epithelium through a cGMP-dependent mechanism tha t 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 cG MP-inhibited phosphodiesterase inhibitor milrinone actually hyperpolar ized 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 i n an increase in amiloride-sensitive sodium absorption, suggesting tha t tonic regulation of amiloride-sensitive sodium absorption is in part due to basal cGMP levels and PKG activity.