title: Processing of atriopeptin prohormone by nonmyocytic atrial cells.
abstract: Atriopeptin (AP) is synthesized and stored in the mammalian atria as a 126 amino acid prohormone (AP126). Upon secretion, the prohormone undergoes site specific proteolysis within the atria to yield the carboxyl terminal 28 amino acid hormone (AP28). The atrial cell responsible for AP126 bioactivation has not yet been determined. Primary neonatal rat atrial cell cultures were generated with and without depletion of nonmyocytic cells. The molecular form of AP detected in the conditioned media of mixed cultures was determined to be AP126. Addition of dexamethasone to these cultures resulted in the appearance of a peptide that co-migrated with AP28. In contrast, no AP126 processing was detected in the conditioned media of myocyte enriched cultures when grown in the presence of dexamethasone. Readdition of nonmyocytic atrial cells to myocyte enriched cultures successfully reconstituted the steroid induced AP126 processing. Incubation of recombinant AP126argarg with nonmyocytic atrial cell cultures resulted in the generation of AP28argarg. We conclude that a nonmyocytic atrial cell is responsible for AP126 processing in vitro.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63108.
authors.forename: J E
authors.initials: JE
authors.lastname: Greenwald
authors.forename: P
authors.initials: P
authors.lastname: Needleman
authors.forename: N
authors.initials: N
authors.lastname: Siegel
authors.forename: E
authors.initials: E
authors.lastname: Tetens
authors.forename: B
authors.initials: B
authors.lastname: Biel
authors.forename: D
authors.initials: D
authors.lastname: Ritter
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria; D006352:Heart Ventricles; D007150:Immunohistochemistry; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D011498:Protein Precursors; D011994:Recombinant Proteins; D003907:Dexamethasone; D009320:Atrial Natriuretic Factor