Arteriovenous Sphingosine-1-Phosphate Differences Across Selected Organs of the Rat

Abstract

Background/Aims: Sphingosine-1-phosphate (S1P) is a bioactive lysosphingolipid that is found in high concentration in plasma. The majority of plasma S1P is transported bound to HDL and albumin. Although the major sources of circulating S1P have been identified, it remains obscure what is the contribution of different organs/tissues to S1P homeostasis in plasma. Answering this question was the major aim of the present study. Methods: The experiment was performed on male Wistar rats from whom blood samples were taken from either: 1) femoral vein, right ventricle of the heart, and abdominal aorta (n=15) or 2) hepatic vein, portal vein, and abdominal aorta (n=11). Plasma was fractionated by sequential flotation ultracentrifugation and sphingolipids were quantified by a HPLC method. Results: Compared to the mixed venous blood sampled from the right ventricle, total plasma and lipoprotein-depleted plasma (LPDP) concentration of S1P in the arterial blood was lower. On the other hand, the level of S1P increased across the leg both in plasma and LPDP. The concentration of S1P, sphingosine, and sphinganine in the plasma, HDL, and LPDP isolated from the blood taken from the hepatic vein was markedly higher compared to both arterial and portal blood. Conclusions: We conclude that, in contrast to HDL-bound S1P, albumin-associated S1P is very labile in the circulation. It is degraded in the pulmonary, and to a lesser extent, gastrointestinal circulation, and released across the liver and skeletal muscle. We also conclude that liver is an important source of HDL-bound S1P and circulating free sphingoid bases.