title: Y-1 adrenocortical tumor cells contain atrial natriuretic peptide receptors which regulate cyclic nucleotide metabolism and steroidogenesis.
abstract: The effects of atrial natriuretic peptide (ANP) on adrenocortical fasciculata cells were examined in the ACTH-responsive Y-1 mouse adrenocortical tumor cell line. Y-1 cell membranes rapidly bound [125I]ANP, with equilibrium binding (22 C) reached within 45 min. Binding of [125I]ANP was inhibited in a concentration-dependent manner by unlabeled ANP and atriopeptin-I (IC50, approximately 1.2 X 10(-9) and 1.6 X 10(-8) M, respectively), but not by C- or N-terminal-deleted ANP fragments, ACTH, or arginine vasopressin (up to 10(-6) M). Scatchard analysis revealed a single class of high affinity binding sites with a Kd of 1.6 X 10(-10) M and a binding capacity of 560 fmol/mg protein. Photo-affinity labeling demonstrated the specific binding of ANP to two protein entities of 130 and 63 kDa. ANP stimulated both cGMP synthesis and secretion from Y-1 cells (EC50, approximately 3.5 X 10(-9) M). Release of the nucleotide was inhibited by probenecid (IC50, approximately 5 X 10(-5) M). The atrial peptide partially inhibited ACTH-stimulated cAMP formation (IC50, approximately 10(-8) M) and partially antagonized basal and ACTH-stimulated steroidogenesis. The data demonstrate the presence in Y-1 cells of specific and saturable ANP receptors, activation of which leads to changes in cyclic nucleotide metabolism and inhibition of steroidogenesis.
authors.affiliation: Unité de Biorégulation Cellulaire, Centre Hospitalier de l'Université Laval, Sainte-Foy, Quebec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Heisler
authors.forename: T
authors.initials: T
authors.lastname: Tallerico-Melnyk
authors.forename: C
authors.initials: C
authors.lastname: Yip
authors.forename: B P
authors.initials: BP
authors.lastname: Schimmer
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology / Q000502:physiology*; D001667:Binding, Competitive; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003345:Corticosterone / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D011339:Probenecid / Q000494:pharmacology; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000502:physiology*
chemical_list: D011956:Receptors, Cell Surface; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009320:Atrial Natriuretic Factor; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP; D011339:Probenecid; D003345:Corticosterone