Factors determining the maximal rate of organic anion secretion by the liver and further evidence on the hepatic site of action of the hormone secretin

Abstract

1. Bromsulphthalein (BSP) was administered throughout the experiments at a constant rate well in excess of its excretory rate, to anaesthetized dogs in which the common bile duct had been cannulated. The maximal excretory rate of BSP into bile (BSP T(m)) obtained in this manner was greatly elevated by choleresis arising from the administration of bile salt (usually taurocholate) at constant rate.2. When bile flow rate was increased in stages by raising the taurocholate administration rate, successive increments in BSP excretion rate were obtained up to a limiting value of about 3 times the original T(m). Beyond this point further increases in taurocholate administration rate caused either no further enhancement of BSP T(m) or a decline in the extent of enhancement produced at a previous lower rate of infusion.3. When taurocholate maximal secretion was established first, the subsequent administration of BSP at progressively increasing rates led to reduction in the taurocholate secretion rate.4. Portal infusion of secretin at constant rate (usually 0.2 units/kg body wt. min) which caused substantial increases in bile flow rate, had no effect on BSP T(m). Increases of bile flow rate of the same order following constant taurocholate infusion produced marked elevation of the BSP T(m).5. These findings are discussed and the following conclusions reached:(a) The limiting factor in BSP maximal transfer is the concentration of BSP in bile; increased bile flow rate at the site of BSP excretion (canaliculi) produced by bile salt administration permits an increase in the original T(m) to occur without the limiting biliary concentration being exceeded.(b) There is excretory competition between BSP and bile salt but over a certain range of bile salt administration the facilitatory effects of increased bile flow rate outweigh the inhibitory effects due to competition.(c) Since secretin administration had no effect on BSP T(m), it is likely that the hydrocholeresis it produces originates downstream from the canaliculi, i.e. in the bile ductules or ducts; this supports previous evidence obtained in a different manner.