EFFECT OF LIPOPOLYSACCHARIDE TREATMENT IN-VIVO ON TISSUE EXPRESSION OF ARGININOSUCCINATE SYNTHETASE AND ARGININOSUCCINATE LYASE MESSENGER-RNAS - RELATIONSHIP TO NITRIC-OXIDE SYNTHASE

Since arginine is the only physiological substrate for the NO synthase reaction, regulation of arginine availability could determine the cel lular rate of NO production, We investigated whether lipopolysaccharid e (LPS) treatment in vivo would alter tissue expression of mRNAs for a rgininosuccinate synthetase (AS) and argininosuccinate lyase (AL), the net action of which is to convert citrulline to arginine. Concomitant with the induction of NO synthase mRNA, injection of LPS into the rat s elicited an increase in AS and AL mRNA levels in the tissues. In con trast with modest increases in the abundance of AS and AL mRNA in lung and heart, a marked increase in levels of AS and AL mRNA in the kidne y occurred. The liver, whether or not treated with LPS, contained high levels of mRNA for AS and AL which are components of the urea cycle. Findings suggest that an increase in the renal capacity to convert cit rulline to arginine could play a key role in NO formation in vivo when arginine becomes limiting. (C) 1995 Academic Press, Inc.