L-arginine uptake, the citrulline-NO cycle and arginase II in the rat brain: an in situ hybridization study

Nitric oxide (NO) is synthesized from a unique precursor, arginine, by nitr ic oxide synthase (NOS). In brain cells, arginine is supplied by protein br eakdown or extracted from the blood through cationic amino acid transporter s (CATs). Arginine can also be recycled from the citrulline produced by NOS activity, through argininosuccinate synthetase (AS) and argininosuccinate lyase (AL) activities, and metabolized by arginase. NOS, AS and AL constitu te the so-called citrulline-NO cycle. In order to better understand arginin e transport, recycling and degradation, we studied the regional distributio n of cells expressing CAT1, CAT3, AS, AL, neuronal NOS (nNOS) and arginase II (AII) in the adult rat brain by non-radioisotopic in situ hybridization (ISH). CAT1, AL and All presented an ubiquitous neuronal and glial expressi on, whereas CAT3 and AS were confined to neurons. nNOS was restricted to sc attered neurons and a few brain nuclei and layers. We demonstrate by this s tudy that cells expressing nNOS all appear to express the entire citrulline -NO cycle, whereas numerous cells expressing AL do not express AS. The diff erential expression of these genes within the same anatomical structure cou ld indicate that intercellular exchanges of citrulline-NO cycle metabolites are relevant. Thus vicinal interactions should be taken into account to st udy their regulatory mechanisms. (C) 1999 Elsevier Science B.V. All rights reserved.