Hyperoxia and paraquat alter the kinetics of platelet serotonin uptake.
Platelets and serotonin (5-HT) have been increasingly implicated in the pathophysiological response to lung microvascular injury. These experiments were undertaken to study the effect of agents known to injure the pulmonary microvasculature on platelet function, i.e., 5-HT uptake kinetics. Mice were exposed to 100% normobaric oxygen (24 to 96 hr) or pretreated ip (3 to 24 hr) with paraquat dichloride (50 mg/kg), diquat dibromide (68 mg/kg), or alpha-naphthylthiourea (ANTU, 10 mg/kg). Mouse platelet 5-HT accumulation was described by a saturable uptake system, possessing high affinity and low capacity, acting in conjunction with passive diffusion. The kinetic constants for the saturable uptake system in control mice were Km 3.37 +/- 0.32 X 10(-7) M and Vmax 46.7 +/- 3.5 pmol 10(8) platelets-1 min-1. Exposure to oxygen for 24 hr resulted in an increased affinity, Km 1.91 +/- 0.67 X 10(-7) M, and a decreased Vmax, 20.0 +/- 5.0 pmol 10(8) platelets-1 4 min-1, with no change in the passive diffusion component. Pretreatment with paraquat (3 hr) produced similar changes (Km 1.71 +/- 0.27 X 10(-7) M and Vmax 15.8 +/- 1.6 pmol 10(8) platelets-1 4 min-1), while diquat and ANTU failed to alter the kinetics of platelet 5-HT uptake. These changes appeared to require a pulmonary toxicant capable of generating a flux of oxygen radicals, and were not due to either the presence of residual toxicant, the presence of an endogenous inhibitor in platelet-rich plasma, or changes in the platelet content of endogenous 5-HT. This study has shown that hyperoxia and paraquat affect platelet function, and suggests that this alteration may contribute to the pathophysiological response of the pulmonary microvasculature to injury produced by these agents.
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004178:Diquat / Q000494:pharmacology; D005609:Free Radicals; D007700:Kinetics; D008297:Male; D051379:Mice; D010100:Oxygen / Q000494:pharmacology*; D010269:Paraquat / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D005609:Free Radicals; D012701:Serotonin; D004178:Diquat; D013890:Thiourea; D010269:Paraquat; D010100:Oxygen; C005277:alpha-naphthyl thiourea