Responses of medaka (Oryzias latipes) ammonia production and excretion to overcome acidified environments.

Anthropogenic acidification of water is an on-going environmental disaster for freshwater fishes. Fishes rely on ammonia excretion to eliminate the excess acid and mitigate the harmful effects; however, it remains largely unknown how ammoniagenesis occurs and is coordinated with ammonia excretion upon acidic stress. Medaka (Oryzias latipes) was used to examine the effects of acidic stress on ammonia production and excretion. We reveal an undiscovered ammonia-producing cell type that is rich in glutaminase (GLS) and located adjacent to the ammonia-excreting ionocytes, Na/H exchanger (NHE) cells, in the gills. The gills, comparing with other ammoniagenetic organs, is the quickest to respond to the acidic stress by triggering GLS-dependent ammonia production. The unique division of labor between GLS and NHE cells in the gills allows medaka to simultaneously upregulate GLS activity and ammonia excretion shortly after exposure to acidic environments. Pharmacological experiment with a GLS inhibitor abolished the activated ammonia excretion, further suggesting the essential role of the unique feature in the responses to acidic stress. Our study shades light on a novel physiological mechanism to timely and efficiently mitigate adverse effects of acidification, providing a new way to assess the impact of on-going environmental acidification on fish.