Many fishes are ammonotelic but some species can detoxify ammonia to glutamine or urea. Certain fish species can accumulate high levels of ammonia in the brain or defense against ammonia toxicity by enhancing the effectiveness of ammonia excretion through active NH4+ transport, manipulation of ambient pH, or reduction in ammonia permeability through the branchial and cutaneous epithelia. Recent reports on ammonia toxicity in mammalian brain reveal the importance of permeation of ammonia through the blood-brain barrier and passages of ammonia and water through transporters in the plasmalemma of brain cells. Additionally, brain ammonia toxicity could be related to the passage of glutamine through the mitochondrial membranes into the mitochondrial matrix. On the other hand, recent reports on ammonia excretion in fish confirm the involvement of Rhesus glycoproteins in the branchial and cutaneous epithelia. Therefore, this review focuses on both the earlier literature and the up-to-date information on the problems and mechanisms concerning the permeation of ammonia, as NH3, NH4+ or proton-neutral nitrogenous compounds, across mitochondrial membranes, the blood-brain barrier, the plasmalemma of neurons, and the branchial and cutaneous epithelia of fish. It also addresses how certain fishes with high ammonia tolerance defend against ammonia toxicity through the regulation of the permeation of ammonia and related nitrogenous compounds through various types of membranes. It is hoped that this review would revive the interests in investigations on the passage of ammonia through the mitochondrial membranes and the blood-brain barrier of ammonotelic fishes and fishes with high brain ammonia-tolerance, respectively.

SUMMARY This study aimed to elucidate the strategies adopted by the African slender lungfish, Protopterus dolloi, to ameliorate the toxicity of ammonia during short (6 days) or long (40 days) periods of aestivation in a layer of dried mucus in open air in the laboratory. Despite decreases in rates of ammonia and urea excretion, the ammonia content in the muscle, liver, brain and gut of P. dolloi remained unchanged after 6 days of aestivation compared with the control fasted for 6 days. For specimens aestivated for 40 days, the ammonia contents in the muscle, liver and gut were significantly lower than those of the control fasted for 40 days, which suggests a decrease in the rate of ammonia production. In addition, there were significant increases in contents of alanine, aspartate and glutamate in the muscle, which suggests decreases in their catabolism. During the first 6 days and the last 34 days of aestivation, the rate of ammonia production was reduced to 26% and 28%, respectively, of the control rate (6.83 μmol day^–1 g^–1 on day 0). During the first 6 days and the next 34 days of aestivation, the averaged urea synthesis rate was 2.39-fold and 3.8-fold, respectively, greater than the value of 0.25 μmol day^–1 g^–1 for the day 0 control kept in water. No induction of activities of the ornithine-urea cycle (OUC) enzymes was observed in specimens aestivated for 6 days, because the suppression of ammonia production led to a light demand on the OUC capacity. For specimens aestivated for 40 days, the activities of carbamoyl phosphate synthetase, ornithine transcarbamylase and argininosuccinate synthetase + lyase were significantly greater than those of the control fasted for 40 days. This is in agreement with the observation that the rate of urea synthesis in the last 34 days was greater than that in the first 6 days of aestivation. P. dolloi aestivated in a thin layer of dried mucus in open air with high O₂ tension throughout the 40 days of aestivation, which could be the reason why it was able to sustain a high rate of urea synthesis despite this being an energy-intensive process. Our results indicate that a reduction in ammonia production and decreases in hepatic arginine and cranial tryptophan contents are important facets of aestivation in P. dolloi.

Ammonia levels in various tissues of the marble goby Oxyeleotris marmoratus remained constant throughout a 72 h period of air exposure. The rate of ammonia excretion in these experimental fish decreased to approximately one-fifth of that of the submerged control. Ammonia was not converted to urea during air exposure because there were no significant increases in urea content in the tissues. Also, urea excretion rate was lowered to one-fiftieth that of the submerged fish. After 24 h of air exposure, there was a significant increase in muscle glutamine content, which peaked at 48 h. The increase in glutamine content could account for the decreases in the amounts of ammonia and urea excretion during air exposure. The specific activities of hepatic glutamate dehydrogenase (amination) and glutamine synthetase in these experimental fish increased threefold and thirtyfold, respectively, in comparison with the submerged controls. Thus, O. marmoratus appears to be the first known teleost that responds to air exposure by activating hepatic glutamine synthetase to detoxify internally produced ammonia.