title: Effects of atrial and brain natriuretic peptides upon cyclic GMP levels, potassium transport, and receptor binding in rat astrocytes.
abstract: The ability of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) to alter cyclic GMP levels and NaKCl cotransport in rat neocortical astrocytes was determined. At concentrations of 10(-9)-10(-6) M, rat ANP99-126 (rANF), rat ANP102-126 (auriculin B), and rat ANP103-126 (atriopeptin III) stimulated 6- to 100-fold increases in cyclic GMP levels. Porcine BNP (pBNP) and rat BNP (rBNP) were 20%-90% as effective as rANF over most of this concentration range, although 10(-6) M pBNP produced a greater effect than rANF. NaKCl cotransport as measured by bumetanide-sensitive 86Rb+ influx was not altered by exposure of astrocytes to 10(-6)M rANF, pBNP, or rBNP. Both pBNP and rBNP, as well as rat ANP103-123 (atriopeptin I) and des[gl18, ser19, gly20, leu21, gly22] ANF4-23-NH2 (C-ANF4-23) strongly competed for specific 125I-rANF binding sites in astrocyte membranes with affinities ranging from 0.03 to 0.4 nM, suggesting that virtually all binding sites measured at subnanomolar concentrations of 125I-rANF were of the ANP-C (ANF-R2) receptor subtype. These receptors are thought to serve a clearance function (Maack et al.: Science 238:675-678, 1987) and may be linked to a guanylate cyclase activity that is chemically and pharmacologically distinct from that coupled to ANP-A (ANF-R1) receptors (Féthiere et al.: Mol Pharmacol 35:584-592, 1989). ANP receptors on astrocytes may function in limiting the access of ANP and BNP to neurons involved in body fluid and cardiovascular regulation.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla 92093.
authors.forename: K
authors.initials: K
authors.lastname: Beaumont
authors.forename: P K
authors.initials: PK
authors.lastname: Tan
mesh_terms: D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D012414:Rubidium Radioisotopes / Q000493:pharmacokinetics
chemical_list: D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D012414:Rubidium Radioisotopes; C058930:brain natriuretic peptide receptor; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP; D011188:Potassium