CONICET | Buscador de Institutos y Recursos Humanos

We investigate the participation of tyrosine kinase, phosphatidylinositol-3-kinase, phospholipase C systems in the intracellular transduction pathways involved in the non genomic stimulation of vasodilators compounds synthesis induced by progesterone. Using aortic strips isolated from female fertile Wistar rats, we showed that physiological concentrations of progesterone markedly increase prostacyclin synthesis in a very short time interval (45 seconds to 10 minutes) as well as nitric oxide release (5 to 30 minutes). The stimulatory action of progesterone on nitric oxide synthase activity was maintained even in the presence of an antagonist of progesterone receptor, compound RU486. In contrast, in the presence of tyrosine kinase inhibitor (1 mM Genistein;) or phosphatidylinositol-3-kinase inhibitor (1 mM LY294002 ), the enhancement of nitric oxide elicited by 10-100nM progesterone was completely suppressed. The steroid stimulates phopholipase C activity, inducing significant increase in diacylglycerol generation (5-15 minutes treatment). The presence of an inhibitor of protein kinase C impaired the antiaggregatory action of the hormone. Due to the fact that phospholipase C activation implies calcium mobilization, we investigate the role of changes in calcium fluxes on progesterone nitric oxide generation. We found that calcium influx from extracellular medium and calcium mobilization from internal pools was required. The present results suggest that, tyrosine kinase and phosphatidylinositol-3-kinase cascades are involved in progesterone nitric oxide synthase stimulation and that diacilglicerol/protein kinase C system may be relevant for physiological regulation of platelet aggregation process.

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