EGTA-INDUCED DISRUPTION OF EPITHELIAL-CELL TIGHT JUNCTIONS IN THE LACTATING CAPRINE MAMMARY-GLAND

The suitability of the Ca2+ chelator ethylene glycol-bis(beta-aminoeth yl ether)-N,N,N',N'-tetraacetic acid (EGTA) to induce disruption of ma mmary tight junctions (TJ) and its effect on milk secretion were inves tigated in six goats. EGTA was administered via the teat of one gland as an isosmotic (300 mosmol/l) K-EGTA solution (68 mM EGTA), whereas t he control gland received an isosmotic sucrose solution. Lactose, Na, K, and Cl in milk, blood lactose, and the presence of Evans blue (EB) in mammary lymph were used as indicators of TJ disruption. EGTA caused transient (approximate to 60 h) changes (P < 0.05) in the concentrati on of lactose, K, Na, and Cl in milk, consistent with loss of TJ integ rity. This was confirmed by a rapid (< 1 h) increase (P < 0.05) in blo od lactose levels. Moreover, EB appeared in lymph < 1 h after EGTA + E B treatment. Milk secretion declined unilaterally by 15% (P < 0.05) af ter EGTA and did not return to baseline until approximate to 60 h afte r EGTA. EGTA caused a unilateral, temporary (first 7 h) increase in ma mmary blood flow. This study shows that a rapid temporary disruption o f mammary TJ can be successfully induced in vivo and that such disrupt ion compromises milk secretion.