EVIDENCE FOR AN INHIBITORY EFFECT OF KALLIKREIN ON COLLECTING DUCT BICARBONATE SECRETION IN RATS AND RABBITS

The luminal membrane of collecting duct cells, especially the intercal ated cells, is normally exposed to active kallikrein. This is the cons equence of the specific localization of this renal enzyme in the conne cting tubule cells and its principal route of secretion being into the tubular lumen. It is conceivable that kallikrein acts downstream on a transporter involved in distal bicarbonate handling. To investigate t his possibility, we estimated bicarbonate concentration and measured k allikrein amidolytic activity in urine fractions collected after a cla ssical stop-flow experiment in rabbits. A highly significant inverse c orrelation was found between these parameters (r=-0.94, p<0.001) in th e peak kallikrein fractions. Neither sodium nor potassium concentratio n were correlated to kallikrein. This suggests that the physiological role of renal kallikrein may be to regulate extracellular fluid pH by inhibiting collecting duct bicarbonate secretion. To test the hypothes is that tubular fluid kallikrein activity and bicarbonate secretion ar e causally related, we developed a novel in vivo stop-flow injection m odel ('orthogade stop-flow'). A hog-kallikrein containing solution (0. 5 mu g/ml) was injected through the abdominal aorta into the renal tub ular system of one kidney of barbiturate-anesthetized rats, while the renal blood supply was interrupted. The ureter was then occluded and r enal blood perfusion reinitiated. After a 2-min contact time five 125- mu l urine fractions were collected. Bicarbonate secretion was clearly detected in the second and third fractions (i.e. those coming from th e collecting ducts) of the control animals, which had received only th e vehicle. There was no bicarbonate secretion peak in the correspondin g urine fractions collected from kallikrein-injected animals. We concl ude that intraluminal kallikrein inhibits collecting duct bicarbonate secretion, probably by inhibiting the chloride/bicarbonate exchanger o f beta-intercalated cells.