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

Bromsulphthalein (BSP) was administered throughout the experiments at a constant rate well in excess of its excretory rate, to anesthetized dogs in which the common bile duct had been cannulated. The maximal excretory rate of BSP into bile (BSP Tm) obtained in this manner was greatly elevated by choleresis arising from the administration of bile salt (usually taurocholate) at constant rate. 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 Tm. Beyond this point further increases in taurocholate administration rate caused either no further enhancement of BSP Tm or a decline in the extent of enhancement produced at a previous lower rate of infusion. When taurocholate maximal secretion was established first, the subsequent administration of BSP at progressively increasing rates led to reduction in the taurocholate secretion rate. 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 Tm. Increases of bile flow rate of the same order following constant taurocholate infusion produced marked elevation of the BSP Tm. 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 Tm to occur without the limiting biliary concentration being exceded, (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 Tm, 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.