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PubMedDate not supplied

Comparison of changes in serotonergic measures in whole blood or plasma and brain in rats given nicotine and/or stresses.

Effects of two kinds of stresses (electric foot shock and water immersion restraint) on serotonergic measures in whole blood or plasma, and whole brain in rats administered with or without nicotine were studied. Plasma tryptophan levels increased after foot shock, but decreased after restraint. Stresses given to nicotine administered rats resulted in decrease in plasma tryptophan levels. Foot shock increased plasma levels of serotonin (5-HT) and restraint decreased its levels in plasma. Plasma and blood 5-hydroxyin-doleacetic acid (5-HIAA) levels increased in rats given stress and nicotine. 5-HIAA/5-HT ratio (turnover rate of 5-HT) in plasma and blood increased only in rats given stresses and nicotine. Increase in 5-HIAA and 5-HIAA/5-HT ratio in all the rats treated were the major changes in brain. There was no parallelism in changes in serotonergic measures between brain and blood or plasma, thus peripheral changes being possibly independent from changes in brain.

Animals↗

PubMedDate not supplied

Novel mechanism to enhance tPA-induced fibrinolysis: effect of limited proteolysis of PAI-1 by neutrophil elastase.

The effect of the proteolytic cleavage of plasminogen activator inhibitor type 1 (PAI-1) by human neutrophil elastase (HNE) on fibrinolysis was investigated. HNE cleaved active recombinant prokaryotic PAI-1 (rpPAI-1) resulting in the formation of low molecular weight forms of rpPAI-1 as previously reported. The latent form of rpPAI-1 was resistant to HNE. NH2-terminal sequence analysis indicated that the cleavage site was Val355-Ser356 (P4-P3). The fact that the strained loop of the latent form of PAI-1 is buried inside the molecule most likely accounts for its resistance to HNE. After the cleavage by HNE, active rpPAI-1 lost its specific activity toward plasminogen activators. The cleavage was both enzyme concentration and time dependent, and the almost complete inactivation of rpPAI-1 (2.9 microM) activity was obtained by a HNE (83 nM) treatment for 30 min at 37 degrees C. Vitroectin partially protected active rpPAI-1 from the HNE digestion. The effect of PAI-1 cleavage by HNE on tissue type PA (tPA) induced clot lysis was studied in a purified system. Clot lysis time without rpPAI-1 was 20.0 +/- 5.0 min, and was prolonged to 86.7 +/- 2.9 min by 68 nM of rpPAI-1. It was shortened when HNE (from 0.6 nM to 80 nM) was added and returned to the value obtained without rpPAI-1 when 80 nM of HNE was present (20.0 +/- 5.8 min). In the absence of PAI-1, however, HNE did not enhance clot lysis at all. The cleavage and inactivation of PAI-1 by HNE was shown to be a novel pathway to enhance fibrinolysis.

Amino Acid Sequence↗