Synthesis and vectorial export of cGMP in airway epithelium: Expression of soluble and CNP-specific guanylate cyclases

C. A. Geary, M. F. Goy, R. C. Boucher

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Guanosine 5'-cyclic monophosphate (cGMP) is an important modulator of fluid balance in many epithelia. We examined its metabolism in primary cultures of human airway epithelia. Sodium nitroprusside increased cGMP levels 30-fold, suggesting that the respiratory epithelium expresses a soluble guanylate cyclase; however, endogenous nitric oxide production was not detected. cGMP levels could also be increased by C-type natriuretic peptide (CNP), but not by atrial natriuretic peptide, brain natriuretic peptide, or Escherichia coli heat-stable enterotoxin, indicating expression of a CNP-specific membrane-bound guanylate cyclase. The one-half effective concentration for CNP was 40 nM and the maximal velocity was 56.7 pmol cGMP·mg protein-1·h-1. After CNP stimulation, ~60% of the total synthesized cGMP was preferentially exported from the polarized epithelial cells across the basolateral membrane by a probenecid-sensitive process. Isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) export revealed a similar export pattern and probenecid sensitivity, although a lower efficiency of export (27% of total cAMP was exported). Consistent with previous reports, export of neither cyclic nucleotide was saturable at the concentrations tested. We conclude that the respiratory epithelium expresses a soluble guanylate cyclase, a CNP-specific receptor, and a novel vectorial cyclic nucleotide export mechanism.

Original languageEnglish (US)
Pages (from-to)L598-L605
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume265
Issue number6 9-6
DOIs
StatePublished - 1993

Keywords

  • C-type natriuretic peptide
  • adenosine 3',5'-cyclic monophosphate
  • cyclic-nucleotide export
  • guanylate cyclase A
  • guanylate cyclase B
  • guanylate cyclase C
  • heat-stable- enterotoxin
  • human respiratory epithelium
  • neutral endopeptidase
  • nitric oxide synthase
  • probenecid

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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