Regional and subcellular distribution of a neutral and basic amino acid transporter in forebrain neurons containing nitric oxide synthase

The neutral and basic amino acid transporter (NBAT) facilitates sodium-inde pendent transport of L-amino acids in renal and intestinal epithelial cells and has been postulated to play a similar role in neurons. In previous stu dies, NEAT has been detected within enteric and brainstem autonomic neurons in a distribution similar to that of constitutive nitric oxide synthase (c NOS). Furthermore, L-arginine, the required precursor for nitric oxide synt hesis, is an excellent NEAT substrate. Together, these findings suggest tha t NEAT may play a role in the regulation of nitric oxide synthesis, through the control of precursor availability. To gain insight into the potential physiological role of NEAT in central neurons, we used an antipeptide antis erum to examine the light and electron microscopic immunocytochemical local ization of NEAT in the rat forebrain and to compare this distribution with that of cNOS. Immunolabeling for NEAT was detected within perikarya and den drite-like processes that were most numerous in the frontal and cingulate c ortex, the ventral striatum, the central amygdala, and the bed nucleus of t he stria terminalis. Labeled varicose axonal processes were distributed mos t densely in the agranular insular cortex and the paraventricular nuclei of the thalamus and hypothalamus (PVH). Electron microscopy showed that immun olabeling for NEAT was distributed along plasmalemmal and vacuolar membrane s within somata, dendrites, and axonal profiles. Many of the NEAT-containin g somata and dendrites contained detectable cNOS. Our results suggest that expression of NEAT may provide specific populations of cNOS-containing fore brain neurons with a unique mechanism for regulating somatodendritic synthe sis of nitric oxide. (C) 1999 Wiley-Liss, Inc.