Discovery of a potent atrial natriuretic peptide antagonist for ANPA receptors in the human neuroblastoma NB-OK-1 cell line

Eur J Pharmacol. 1992 Dec 2;224(2-3):183-8. doi: 10.1016/0014-2999(92)90803-c.


The effects of seven competitive atrial natriuretic peptide (ANP) receptor antagonists were compared on cultured human neuroblastoma NB-OK-1 cells expressing exclusively ANPA receptors, by evaluating their capacity to inhibit [125I]ANP binding and to suppress ANP-stimulated cyclic GMP elevation. In ANP analogues with a shortened Cys7-Cys18 bridge, Asp13 and a hydrophobic Tic residue at position 16 expressed antagonistic activity, while Ala16 provoked lower antagonistic potency and Phe16 induced receptor activation. The binding affinity of A71915 ([Arg6, Cha8]ANP-(6-15)-D-Tic-Arg-Cys-NH2), the most potent antagonist (with a pKi of 9.18 and a pA2 of 9.48) was only 22 times less lower than that of the agonist ANP-(1-28).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atrial Natriuretic Factor / metabolism
  • Atrial Natriuretic Factor / pharmacology
  • Binding Sites
  • Cyclic GMP / metabolism
  • Humans
  • Neuroblastoma
  • Neurons / drug effects*
  • Neurons / metabolism
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Receptors, Atrial Natriuretic Factor / antagonists & inhibitors*
  • Receptors, Atrial Natriuretic Factor / metabolism
  • Tetrahydroisoquinolines
  • Tumor Cells, Cultured


  • Peptide Fragments
  • Tetrahydroisoquinolines
  • A 71915
  • Atrial Natriuretic Factor
  • Receptors, Atrial Natriuretic Factor
  • Cyclic GMP