Ammonia stimulates glutamine uptake to the cerebral non-synaptic mitochondria of the rat

The uptake of [3H]glutamine (GLN) to non-synaptic mitochondria isolated from rat cerebral hemispheres was measured in the absence or presence of 3 mM ammonium ion (ammonium chloride; ammonia). Ammonia increased Vmax of the saturable component of GLN uptake by > 20%, without affecting K(m), but did not change a non-saturable component of GLN transport representing diffusion or uptake mediated by a very low affinity carrier. Since GLN is an idiogenic osmole, its increased uptake may contribute to the swelling of astrocytic mitochondria and, subsequently, to a decrease in cerebral energy metabolism usually associated with acute hyperammonemic states. The result is consistent with the recent view that GLN accumulating in the brain in hyperammonemic conditions contributes to ammonia neurotoxicity.