In vivo effects of colchicine on milk fat globule membrane

Milk secretion in lactating goats was suppressed reversibly by infusing colchicine (2.5 to 5 mg) into one half of the udder via the teat canal. Fat globules were isolated from milks before, during and after (96 h post-infusion) this suppression. Protein, phospholipid, cholesterol (free and esterified), 5'-nucleotidase activity and peptide patterns by gel electrophoresis of these globule samples were determined. Association of [14C]colchicine with milk fat globules in vivo and in vitro also was investigated. Amounts of protein, phospholipid and free cholesterol per g of globule and 5'-nucleotidase per mg of globule protein fall following colchicine infusion. The nature of these changes suggests that the supply of membrane for milk secretion is restricted as a result of the drug treatment. Patterns of globule peptides by gel electrophoresis were qualitatively similar during the experimental period. However, a major globule glycoprotein, Mr = 52 000, showed a significant (3-fold) increase relative to the other principal peptide bands during the period of reduced milk flow. Analysis of milks for radioactivity following infusion of [14C]colchicine revealed that a portion of activity returning in milk is associated with fat globules. This activity peaked at 72 h post-infusion. Evaluation of [14C]colchicine binding to milk fat globules in vitro yielded evidence that the drug binds to the cytoplasmic, but not the exterior surface of the globule membrane. Colchicine's inhibition of milk synthesis and secretion is discussed.