Cadmium inhibits vacuolar H(+)ATPase-mediated acidification in the rat epididymis

In rats, an acidic luminal pH maintains sperm quiescence during storage in the epididymis. We recently showed that vacuolar H(+)ATPase-rich cells in t he epididymis and vas deferens are involved in the acidification of these s egments. Treatment of rats with cadmium (Cd) leads to alkalinization of thi s fluid by an unknown mechanism. Because Cd may affect H(+)ATPase function, we examined 1) the in vivo effect of Cd poisoning on H(+)ATPase-rich cell morphology and on the abundance and distribution of the 31-kDa H(+)ATPase s ubunit in cells along the rat epididymis, and 2) the in vitro effect of Cd on H(+)ATPase activity and function in the isolated vas deferens. Immunoflu orescencce and immunoblotting data from rats treated with Cd for 14-15 days (2 mg Cd/kg body mass/day) showed that 1) H(+)ATPase-positive cells regres sed to a prepubertal phenotype, and 2) H(+)ATPase was lost from the apical pole of the cell and was redistributed into an intracellular compartment. I n experiments in vitro, Cd inhibited bafilomycin-sensitive ATPase activity in isolated total cell membranes and, as measured using a proton-selective extracellular microelectrode, inhibited proton secretion in isolated vas de ferens. We conclude that alkalinization of the tubule fluid in the epididym is and vas deferens of Cd-treated rats may result from the loss of function al H(+)ATPase enzyme in the cell apical domain as well as from a direct inh ibition of H(+)ATPase function by Cd.