Cloning, characterization, and functional expression of a CNP receptor regulating CFTR in the shark rectal gland.

Academic Article

Abstract

  • In the shark, C-type natriuretic peptide (CNP) is the only cardiac natriuretic hormone identified and is a potent activator of Cl- secretion in the rectal gland, an epithelial organ of this species that contains cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels. We have cloned an ancestral CNP receptor (NPR-B) from the shark rectal gland that has an overall amino acid identity to the human homologue of 67%. The shark sequence maintains six extracellular Cys present in other NPR-B but lacks a glycosylation site and a Glu residue previously considered important for CNP binding. When shark NPR-B and human CFTR were coexpressed in Xenopus oocytes, CNP increased the cGMP content of oocytes (EC50 12 nM) and activated CFTR Cl- channels (EC50 8 nM). Oocyte cGMP increased 36-fold (from 0.11 +/- 0.03 to 4.03 +/- 0.45 pmol/oocyte) and Cl- current increased 37-fold (from -34 +/- 14 to -1,226 +/- 151 nA) in the presence of 50 nM CNP. These findings identify the specific natriuretic peptide receptor responsible for Cl- secretion in the shark rectal gland and provide the first evidence for activation of CFTR Cl- channels by a cloned NPR-B receptor.
  • Published In

    Keywords

  • Amino Acid Sequence, Animals, Chlorides, Cloning, Molecular, Cystic Fibrosis Transmembrane Conductance Regulator, Dogfish, Electrophysiology, Female, Guanylate Cyclase, Humans, Male, Molecular Sequence Data, Nucleotides, Cyclic, Oocytes, RNA, Messenger, Receptors, Atrial Natriuretic Factor, Salt Gland, Xenopus
  • Digital Object Identifier (doi)

    Author List

  • Aller SG; Lombardo ID; Bhanot S; Forrest JN
  • Start Page

  • C442
  • End Page

  • C449
  • Volume

  • 276
  • Issue

  • 2