title: Natriuretic peptides induce weak VASP phosphorylation at Serine 239 in platelets.
abstract: Cyclic guanosine-3',5'-monophoshate (cGMP) is the common second messenger for the cardiovascular effects of nitric oxide (NO) and natriuretic peptides (NP; e.g. atrial NP [ANP]), which activate soluble and particulate guanylyl cyclases, respectively. The role of NO in regulating cGMP and platelet function is well documented, whereas there is little evidence supporting a role for NPs in regulating platelet reactivity. By studying platelet aggregation and secretion in response to a PAR-1 peptide, collagen and ADP, and phosphorylation of the cGMP-dependent protein kinase (PKG) substrate vasodilator-stimulated phosphoprotein (VASP) at serine 239, we evaluated the effects of NPs in the absence or presence of the non-selective cGMP and cAMP phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX). Our results show that NPs, possibly through the clearance receptor (natriuretic peptide receptor-C) expressed on platelet membranes, increase VASP phosphorylation but only following PDE inhibition, indicating a small, localised cGMP synthesis. As platelet aggregation and secretion measured under the same conditions were not affected, we conclude that the magnitude of PKG activation achieved by NPs in platelets per se is not sufficient to exert functional inhibition of platelet involvement in haemostasis.
authors.affiliation: Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham , Birmingham , UK.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Borgognone
authors.forename: Kate L
authors.initials: KL
authors.lastname: Lowe
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Watson
authors.forename: Melanie
authors.initials: M
authors.lastname: Madhani
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000097:blood*; D006152:Cyclic GMP / Q000096:biosynthesis / Q000097:blood; D017869:Cyclic GMP-Dependent Protein Kinases / Q000097:blood; D006801:Humans; D008840:Microfilament Proteins / Q000097:blood*; D045265:Natriuretic Peptides / Q000097:blood / Q000494:pharmacology*; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010750:Phosphoproteins / Q000097:blood*; D010766:Phosphorylation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D045265:Natriuretic Peptides; D010446:Peptide Fragments; D010726:Phosphodiesterase Inhibitors; D010750:Phosphoproteins; C082835:thrombin receptor peptide (42-47); D000098662:Vasodilator-Stimulated Phosphoprotein; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D015056:1-Methyl-3-isobutylxanthine