title: Potentiation of platelet aggregation by atrial natriuretic peptide.
abstract: Atrial natriuretic peptide (ANP) has binding sites on a variety of tissues, including human platelets. We have used a new, quenched-flow approach coupled to single-particle counting to investigate the effects of ANP (rat, 1-28) on the initial events (within the first several seconds) following human platelet activation. While ANP alone (1 pM-100 nM) had no effect, ANP significantly potentiated thrombin (0.4 units/ml)-, epinephrine (15 microM)- and ADP (2 or 10 microM)-induced aggregation. Maximum stimulation occurred between 10 to 100 pM. ANP had no influence on the thrombin or ADP-induced increase in platelet volume associated with the "shape change." Since ANP receptors are coupled to a particulate guanylate cyclase and some ANP-induced effects may be mediated through cyclic GMP, we studied how another activator of platelet guanylate cyclase, sodium nitroprusside, affected platelet activation and cyclic nucleotide levels. Sodium nitroprusside (1 microM) inhibited ADP, but not thrombin or epinephrine-induced aggregation. Both sodium nitroprusside (1 microM) and ANP (10 nM) increased cyclic GMP levels by 80% and 37%, respectively, within 60 sec in washed platelets. ANP had no effect on platelet cyclic AMP, while sodium nitroprusside induced a 77% increase. These data suggest that the platelet ANP receptor may be coupled to guanylate cyclase and the rise in cyclic GMP may potentiate platelet function.
authors.affiliation: Department of Pharmacology, University of Virginia School of Medicine, Charlottesville 22908.
authors.forename: A L
authors.initials: AL
authors.lastname: Loeb
authors.forename: A R
authors.initials: AR
authors.lastname: Gear
mesh_terms: D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001665:Binding Sites; D006152:Cyclic GMP / Q000097:blood; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D009599:Nitroprusside / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D013917:Thrombin / Q000494:pharmacology
chemical_list: D009599:Nitroprusside; D009320:Atrial Natriuretic Factor; D013917:Thrombin; D006152:Cyclic GMP; D004837:Epinephrine