Arginosuccinate synthetase, arginosuccinate lyase and NOS in canine gastrointestinal tract: immunocytochemical studies.

Nitric oxide synthase (NOS) requires the substrate L-arginine for NO production to support multiple gastrointestinal functions. We asked, 'Where do enzymes to regenerate L-arginine from L-citrulline exist?'. We examined loci of immunoreactivities in the canine gastrointestinal tract for arginosuccinate synthetase and arginosuccinate lyase, enzymes that resynthesize L-arginine from L-citrulline, in relation to the distribution of nNOS immunoreactivity or NADPH-diaphorase histochemistry. Arginosuccinate synthetase and lyase were present in many neurones and nerve fibres in the myenteric plexus of the lower oesophageal sphincter (LOS), antrum, pylorus, ileum and colon; in the submucosal plexus of ileum and colon; in longitudinal muscle of ileum and colon; and in nerve bundles in circular muscle everywhere. LOS muscle was also immunoreactive for both enzymes. Circular and longitudinal muscle cells of the ileum and colon and cells resembling interstitial cells of Cajal in the deep muscular plexus of the ileum and the submuscular plexus of the colon also appeared immunoreactive. In neurones, arginosuccinate synthetase and nNOS were usually co-localized. NADPH diaphorase activity was present in LOS and likely in pylorus, but not in muscularis externa of ileum or colon. We conclude that resynthesis of L-arginine probably occurs in enteric nerves, interstitial cells of Cajal (ICC) and LOS muscle; also apparently in some cells without NOS to utilize it.