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Atrial natriuretic peptide binds to ANP-R1 receptors in neuroblastoma cells or is degraded extracellularly at the Ser-Phe bond.

Abstract
ANP-R1 receptors for atrial natriuretic peptide (ANP) showed the following rank order of affinity in intact human neuroblastoma cells NB-OK-1: human ANP-(99-126) approximately human ANP-(102-126) approximately rat ANP-(99-126) (K1 17-32 pM) > human ANP-(103-126) > porcine brain natriuretic peptide (BNP). Analogues truncated at the C-terminal extremity or devoid of a disulphide bridge, such as rat ANP-(103-123), rat C-ANP-(102-121), rat ANP-(111-126), rat ANP-(99-109) and rat [desCys105,Cys121]ANP-(104-126) and chicken C-type natriuretic peptide, were not recognized. The occupancy of these high affinity ANP-R1 receptors led to marked cyclic GMP accumulation in the presence of 3-isobutyl 1-methylxanthine. An ectoenzymic activity, partly shed in the incubation medium, provoked the stepwise release of Phe-Arg-[125I]Tyr, Arg-[125I]Tyr and [125I]Tyr from rat [125I]ANP-(99-126), at an optimal pH of 7.0. Its inhibition by 1,10-phenanthroline, EDTA and bacitracin but not by thiorphan suggests the contribution of at least one neutral metalloendopeptidase, distinct from EC 3.4.24.11, for which ANP showed high affinity.
AuthorsC Delporte, P Poloczek, M Tastenoy, J Winand, J Christophe
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 227 Issue 3 Pg. 247-56 (Nov 02 1992) ISSN: 0014-2999 [Print] Netherlands
PMID1335413 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Iodine Radioisotopes
  • Peptide Fragments
  • Atrial Natriuretic Factor
  • L-Lactate Dehydrogenase
  • Metalloendopeptidases
  • Receptors, Atrial Natriuretic Factor
  • Cyclic GMP
Topics
  • Animals
  • Atrial Natriuretic Factor (metabolism, pharmacology)
  • Cell Survival
  • Chickens
  • Chromatography, High Pressure Liquid
  • Cyclic GMP (analysis)
  • Dose-Response Relationship, Drug
  • Humans
  • Hydrogen-Ion Concentration
  • Iodine Radioisotopes
  • L-Lactate Dehydrogenase (analysis)
  • Metalloendopeptidases (metabolism)
  • Neuroblastoma (metabolism)
  • Peptide Fragments (metabolism)
  • Rats
  • Receptors, Atrial Natriuretic Factor (metabolism)
  • Swine
  • Tumor Cells, Cultured

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