Intimal Platelets are thought to play a major role in the formation of arterial intimal lesions (1, 2) by releasing, at sites of endothelial denudation, growth factors that stimulate smooth muscle cell (SMC) growth. Support for the role of platelets in vivo comes from the key study of Friedman et al. (3), in which these authors showed that experimentally induced intimal lesion formation in rabbit arteries was significantly inhibited by prolonged thrombocytopenia. This study was interpreted by others to suggest that platelets play an important role in the induction of SMC replication, even though no cell cycle data were presented. An alternative hypothesis is that platelets and their mitogens were important in initiating migration of cells into the intima. In this regard, platelet-derived growth factor (PDGF) has been shown to be chemotactic for mesenchymal cells (4,5). The goal of this study was to determine whether, after balloon catheter denudation, inhibition of platelet adherence influenced SMCs in terms of early mRNA expression and cell proliferation. To accomplish this, we used a single injection of a polyclonal antibody against rat platelets that prevented their adherence to the subendothelium for more than 24 hr after injury. Using this protocol, we were able to show that the absence of platelets did not affect the early proliferation of SMCs in response to injury but did inhibit formation of intimal lesions. We conclude that after balloon catheter injury platelets play a minor role in promoting medial proliferation but are important in the stimulation of SMC migration into the intima.
We have examined the effects of adenosine on sodium-coupled phosphate and glucose transport in cultured opossum kidney (OK) cells, a continuous cell line that resembles proximal tubule. Adenosine analogues R-(-)-N6-phenylisopropyladenosine (PIA) and 2',5'-dideoxy-adenosine (DDA) were employed as adenosine A1 receptor and P site-selective agonists, respectively. Sodium-dependent phosphate uptake activity (Na-Pi symport) increased by approximately 25% above both basal and parathyroid hormone (PTH)-inhibited levels in cells treated with PIA (0.1, 1 microM) but not in cells treated with DDA (100 microM). Adenosine (PIA) also stimulated sodium-coupled 3-O-methylglucose transport by approximately 40%. Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) content was inversely related to Na-Pi symport activity in cells treated with PIA and PTH. However, changes in Na-Pi symport activity did not consistently relate to changes in intracellular cAMP. Protein kinase C was activated 15 s after treatment of OK cells with 1 microM PIA. Preincubation of cells with 3 microM staurosporine attenuated the effect of 1 microM PIA on phosphate uptake. These data suggest that Na-Pi and Na-glucose symport activities are stimulated by adenosine acting at a receptor coupled to more than one intracellular signal. It is likely that both protein kinases A and C are involved in these actions of adenosine.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.