The secretion of citrate into milk.

1. The time course of changes in specific activities of citrate, lactose and fatty acids in milk during frequent milking, following the I.V. administration of labelled glucose, acetate and chylomicrons in goats has been studied. Peak specific activities of lactose and citrate in milk were reached at 2-3 hr, while peak specific activites of fatty acids were reached at 5-7 hr. 2. Following short I.A. infusions of 24Na, 36Cl, and 42K, peak specific activities in milk were reached in 1 hr or less. 3. The mammary epithelium of lactating goats was found to be virtually impermeable to labelled citrate in both directions. 4. Labelled citrate had an apparent volume of distribution in lactating guinea-pigs mammary slices in vitro similar to that of extracellular space markers. 5. Treatment of goats with large doses of oxytocin markedly increased the permeability of the secretory epithelium to labelled citrate. 6. In the goat mammary gland, citrate, protein and calcium failed to enter milk which had been diluted with isosmotic lactose by intraductal injection, whereas Na, K and Cl did enter, thus tending to restore the concentrations of these ions to normal. 7. It is suggested that citrate, which is formed within the sucretory cell, enters milk not by passage across the apical cell membrane but, in common with lactose and milk protein, by exocytosis of Golgi vesicles. It appears that citrate is held at high concentrations in milk by virtue of the impermeability of the mammary epithelium to the forms in which it occurs in milk.