The primary structure of a plasma membrane guanylate cyclase demonstrates diversity within this new receptor family

Cell. 1989 Sep 22;58(6):1155-62. doi: 10.1016/0092-8674(89)90513-8.


Atrial natriuretic peptide (ANP) binds directly to a plasma membrane form of guanylate cyclase (GC-A), stimulating the production of the second messenger cyclic GMP. We show that a second guanylate cyclase/receptor (GC-B) exists, with distinctly different specificities for various natriuretic peptides. A cDNA clone encoding GC-B was isolated by low-stringency screening of a rat brain cDNA library using GC-A cDNA as a probe. The deduced amino acid sequence of GC-B is 78% identical with GC-A within the intracellular region, but 43% identical within the extracellular domain. Cyclic GMP concentrations in cells transfected with GC-A were half-maximally elevated at 3 nM ANP, 25 nM brain natriuretic peptide (BNP), and 65 nM atriopeptin 1, while 25 microM ANP, 6 microM BNP, and greater than 100 microM atriopeptin 1 were required for half-maximal stimulation of GC-B. The potencies of natriuretic peptides on GC-A and GC-B activity are therefore markedly different; furthermore, despite the specificity of GC-B for BNP, the relatively high BNP concentration required to elicit a response suggests the possible presence of a more potent, unidentified natural ligand.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Atrial Natriuretic Factor / metabolism
  • Base Sequence
  • Brain / enzymology
  • Cell Line
  • Cell Membrane / enzymology
  • Cloning, Molecular
  • DNA / genetics
  • Genes*
  • Genetic Variation
  • Guanylate Cyclase / genetics*
  • Molecular Sequence Data
  • Multigene Family*
  • Nucleic Acid Hybridization
  • Rats
  • Receptors, Atrial Natriuretic Factor
  • Receptors, Cell Surface / genetics*
  • Sequence Homology, Nucleic Acid
  • Transfection


  • Receptors, Cell Surface
  • Atrial Natriuretic Factor
  • DNA
  • Guanylate Cyclase
  • Receptors, Atrial Natriuretic Factor

Associated data

  • GENBANK/M26896