Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effects of BN 50739, a novel PAF antagonist, in a rat model of traumatic shock. Pentobarbital anesthetized rats subjected to Noble-Collip drum trauma developed a shock state characterized by marked hypotension, significant increases in plasma cathepsin D (4.2-fold), free amino-nitrogen (2.8-fold) and myocardial depressant factor (4.7-fold) activities and a survival time of 1.62 +/- 0.16 h. Treatment with BN 50739 (10 mg/kg, i.v.) 10 min post-trauma prolonged survival time to 3.14 +/- 0.44 h (p less than 0.01) and attenuated the accumulations of cathepsin D (5.8 vs. 12.5 U/ml, p less than 0.01), free amino-nitrogen (4.6 vs. 12.5 U/ml, p less than 0.001) and myocardial depressant factor (19.4 vs. 65.1 U/ml, p less than 0.001). Moreover, in washed rabbit platelets, BN 50739 inhibited PAF (1.85 nM)-induced aggregation (IC50: 50 nM) without affecting ADP (5 microM)-induced aggregation. In anesthetized rats, BN 50739 (10 mg/kg, i.v.) attenuated PAF (10-30 ng/kg, i.v.)-induced hypotension for longer than 5 h, without influencing acetylcholine (10 micrograms/kg, i.v.)-induced hypotension. These findings indicate that BN 50739 is a specific PAF receptor antagonist with a long duration of action in vivo. The beneficial effects of PAF antagonism on traumatic shock are significant in the present study, and are consistent with the concept that PAF is involved in the pathogenesis of traumatic shock.
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PMID:Beneficial actions of BN 50739, a new PAF receptor antagonist, in murine traumatic shock. 216 4

We studied RO 15-1788, a new benzodiazepine receptor antagonist, [ethyl 8-fluoro-5, 6-dihydro-5-methyl-6-oxo-4H-imidazo (1, 5a) (1, 4) benzodiazepine-3-carboxylate] to determine its effects in a murine model of hemorrhagic shock. Hemorrhaged rats treated with RO 15-1788 maintained post-reinfusion mean arterial blood pressure (MABP) at significantly higher values compared to rats receiving only the vehicle (final MABP 114 +/- 4 vs 82 +/- 4 mmHg, p less than 0.001). Moreover, RO 15-1788 decreased the release of the lysosomal hydrolase, cathepsin D (p less than 0.02) into the circulation and blunted the plasma accumulation of free amino-nitrogen groups (p less than 0.01). Furthermore, the plasma activity of a myocardial depressant factor (MDF) was significantly lower in RO 15-1788 treated rats subjected to hemorrhagic shock than in those given the vehicle (18 +/- 2 vs 42 +/- 4 U/ml, p less than 0.01). Additionally, in vitro analysis indicated that RO 15-1788 antagonizes PAF induced coronary vasoconstriction and cardiac depression observed in perfused rat hearts, as well as inhibiting PAF induced platelet aggregation in cat platelet rich plasma. Our results suggest that antagonism of PAF actions can contribute significantly to the beneficial effects of RO 15-1788 in hemorrhagic shock.
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PMID:Beneficial actions of RO 15-1788, a benzodiazepine receptor antagonist, in hemorrhagic shock. 311 57