(i.e. the total of NH3
) is highly toxic in most animals. Hydrated NH4+
ions have the same ionic radius (Knepper et al., 1989
) and due to their K+
-like behavior, ammonium ions affect the membrane potential for example, in the giant axon of Loligo pealei
(Binstock and Lecar, 1969
) and of mammalian neurons (Cooper and Plum, 1987
). In mammals, elevated ammonia causes major damage in the central nervous system, including changes in blood–brain barrier morphology (Laursen and Diemer, 1997
). In addition, elevated ammonia levels in mammals have been related to Alzheimer disease (Alzheimer Type II astrocytosis) due to toxic accumulation of glutamine in astrocytes, which leads to cell swelling and cell death (for review see Butterworth, 2002
). Also, in microglia and astroglioma cell lines, ammonia affects major functional activities, such as phagocytosis and endocytosis. Ammonia also modifies the release of cytokines and increases the activity of lysosomal hydrolases (Atanassov et al., 1994
). Marcaida et al. (1992
) speculated that ammonia toxicity is mediated by excessive activation of N
-methyl-D-aspartate (NMDA)-type glutamate receptors in the brain. As a consequence, cerebral ATP depletes while intracellular Ca2+
increases with subsequent increases in extracellular K+
and finally cell death.
In crustaceans, for example in the lobster Homarus americanus (Young-Lai et al., 1991) and the crayfish Pacifastacus leniusculus (Harris et al., 2001), elevated ammonia levels in low-salinity media disrupt ionoregulatory function. Exposure of the green shore crab Carcinus maenas to 1 mmol l–1 total ammonia leads to increased ion permeability and salt flux across the gill; higher concentrations reduce both variables (Spaargaren, 1990). In fish, branchial gas exchange and oxidative metabolism are disturbed by excess ammonia (Wilkie, 1997).
An effective ammonia detoxification or excretion system is, therefore, essential to maintain cellular functions, and to keep cellular and body fluid ammonia levels within a tolerable range. In most species, including mammals (Cooper and Plum, 1987), fish (Wood et al., 2002) and aquatic crabs (Cameron and Batterton, 1978; Weihrauch et al., 1999), the ammonia concentration of the body fluids is typically low (50–400 µmol l–1; Table 1). Concentrations exceeding 1 mmol l–1 total ammonia (NH3+NH4+) are usually toxic to mammalian cells (Hrnjez et al., 1999). In crustaceans, environmental exposure of ammonia is lethal at relatively low doses. For instance, LC50 after 96 h of exposure was determined in the crayfish Orconectes nais at 186 µmol l–1 NH3 (Hazel et al., 1982), in the Sao Paulo shrimp Penaeus paulensis at 19 µmol l–1 NH3 and 0.307 mmol l–1 total ammonia (Ostrensky et al., 1992) and in the redtail prawn Penaeus penicillatus 58 µmol l–1 NH3 and 1.39 mmol l–1 total ammonia (Chen and Lin, 1992).
Mammals accrue ammonia both from metabolism and as an influx to the hepatocytes from the gastrointestinal tact. This ammonia is detoxified in the urea cycle, an energy-consuming process, by incorporation into the less-toxic urea. Crustaceans are largely ammonotelic, aquatic species exclusively so, and in water excrete their nitrogenous waste directly to the environment as highly soluble ammonia.