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

Abstract

We investigated the role of platelet-activating factor (PAF) as a mediator of system A amino acid transport alterations in skeletal muscle during endotoxic shock. Male Sprague-Dawley rats (80-100 g) were injected with Salmonella enteritidis endotoxin (10 mg/kg intravenously (i.v.)) or PAF (4 micrograms/kg i.v.) and killed 5 or 1 h later, respectively. Control rats were injected with a vehicle. System A amino acid transport was assessed by measuring the cellular uptake of 1-14C-alpha-aminoisobutyric acid (AIB, amino acid analog) in isolated soleus and extensor digitorum longus (EDL) muscles, in vitro. AIB uptake in soleus and EDL 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 administration of WEB 2086 (30 mg/kg i.v.), a PAF receptor antagonist, attenuated the endotoxin-induced inhibition of amino acid transport by 26% in EDL and 17% in soleus. PAF (1 microgram/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 micrograms/kg) and after incubation in media containing PAF (1 microgram/mL). Addition of plasma to incubation 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.(ABSTRACT TRUNCATED AT 250 WORDS)