Discovery of a potent atrial natriuretic peptide antagonist for ANPA receptors in the human neuroblastoma NB-OK-1 cell line.
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).
Delporte
C
C
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Brussels, Belgium.
Winand
J
J
Poloczek
P
P
Von Geldern
T
T
Christophe
J
J
D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044005:Tetrahydroisoquinolines; D014407:Tumor Cells, Cultured
D010446:Peptide Fragments; D044005:Tetrahydroisoquinolines; C078792:A 71915; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP