Effects of ATP, ADP, thrombin, vasopressin and U46619 on human placental nitric oxide synthase activity.
The human placenta contains nitric oxide synthase (NOS) activity, which had been previously found to be localized in the syncytiotrophoblast and the endothelial cells of stem villous vessels. Nitric oxide produced by the syncytiotrophoblast could affect maternal platelet aggregation. The aim of the present study was to examine the effects of substances known to cause platelet aggregation (arginine vasopressin (AVP), the thromboxane A2 mimetic U46619, adenosine diphosphate (ADP) and thrombin) on NOS activity of human placental explants in vitro. Placentae were obtained at term from women with obstetrically uncomplicated deliveries. NOS activity was measured in explants by determining the conversion of [3H]L-arginine to [3H]L-citrulline during 60 min incubations. Either the presence of N-omega-L-arginine or the omission of calcium (in the presence of EDTA) significantly inhibited NOS activity. Adenosine triphosphate (ATP) at concentrations of 100-1000 microM significantly stimulated NOS activity, and was used as a positive control. ADP at a concentration of 1000 microM was found to significantly stimulate NOS activity, however, the other platelet aggregating substances investigated, thrombin (0.1, 10 U/ml), AVP (1, 10, 20 microM) and U46619 (3, 30, 300 nM), had no significant effect on NOS activity. These results show that ATP and ADP can stimulate human placental NOS activity, but provide no evidence that platelet aggregating agents other than ADP can affect the production of NO.
Di Iulio
J L
JL
Department of Perinatal Medicine, Royal Women's Hospital, Carlton, Victoria, Australia.
Gude
N M
NM
Brennecke
S P
SP
King
R G
RG
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D001120:Arginine / Q000378:metabolism; D002855:Chromatography, Thin Layer; D002956:Citrulline / Q000378:metabolism; D005260:Female; D006490:Hemostatics / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology; D013917:Thrombin / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology*
D006490:Hemostatics; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D019335:Nitroarginine; D002956:Citrulline; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D001120:Arginine; D019001:Nitric Oxide Synthase; D013917:Thrombin