THE ROLE OF PLATELET-ACTIVATING-FACTOR IN ALTERATIONS OF SYSTEM-A AMINO-ACID-TRANSPORT IN RAT SOLEUS AND EXTENSOR DIGITORUM-LONGUS MUSCLES DURING ENDOTOXIC-SHOCK

We investigated the role of platelet-activating factor (PAF) as a medi ator of system A amino acid transport alterations in skeletal muscle d uring endotoxic shock. Male Sprague-Dawley rats (80-100 g) were inject ed with Salmonella enteritidis endotoxin (10 mg/kg intravenously (i.v. )) or PAF (4 mu g/kg i.v.) and killed 5 or 1 h later, respectively. Co ntrol rats were injected with a vehicle. System A amino acid transport was assessed by measuring the cellular uptake of 1-C-14-alpha-aminois obutyric acid (AIB, amino acid analog) in isolated soleus and extensor digitorum longus (EDL) muscles, in vitro. AIB uptake in soleus and ED L from endotoxic rats was approximately 33% lower than control muscles . The i.v. injection of PAF reduced AIB uptake 9% in soleus and 15% in EDL as compared with muscles from control rats. The prophylactic admi nistration of WEB 2086 (30 mg/kg i.v.), a PAF receptor antagonist, att enuated the endotoxin-induced inhibition of amino acid transport by 26 % in EDL and 17% in soleus. PAF (1 mu g/mL) added to incubation media had no effect on AIB uptake in soleus and EDL of control rats. However , there was a reduction in AIB uptake in soleus and EDL obtained from rats 1 h after an i.v. injection of PAF (4 mu g/kg) and after incubati on in media containing PAF (1 mu g/mL). Addition of plasma to incubati on media obtained from rats 1 h after the i.v. injection of endotoxin or PAF attenuated AIB uptake in soleus and EDL of control rats. The fi ndings of this study suggest that 1) PAF is, in part, responsible for the attenuation of system A amino acid transport in skeletal muscle du ring endotoxic shock; 2) PAF attenuates amino acid transport in skelet al muscle due to conditions and/or factors released in plasma that may be similar to those existing during endotoxic shock; and 3) the direc t inhibition of amino acid transport in vitro by PAF depends upon prev ious exposure of skeletal muscle to those conditions or factors genera ted by PAF in vivo.