Pharmacologic Effect of Somatostatin on Bile Formation in the Dog

Abstract

A study was carried out to define the effect of somatostatin on bile secretion using a chronic bile fistula dog preparation. Bile flow, erythritol clearance, and biliary electrolyte and lipid composition were measured under steady-state conditions during four randomized treatments: placebo, somatostatin, cimetidine, and cimetidine + somatostatin. In addition, the effect of three increasing doses of secretin was defined during each treatment. A constant cholyltaurine infusion was used to compensate for the interrupted enterohepatic circulation of bile acids. Somatostatin caused a consistent reduction in total bile flow and biliary bicarbonate output, but its effect on canalicular bile flow, as assessed by erythritol clearance, was variable. Outputs of bile acids, lecithin, and cholesterol remained unchanged during the somatostatin infusion. Because the bile/plasma ratio of erythritol concentration increased greatly during somatostatin infusion, the reduction in bile flow was attributed to enhanced ductular reabsorption (or alternatively, decreased ductular secretion) of a fluid whose calculated electrolyte composition was identical to that induced by secretin infusion in the control group. Secretin and somatostatin antagonized each other's effects: at a low dose of secretin, somatostatin caused decreased bile volume, whereas the highest dose of secretin effectively antagonized the effect of somatostatin. The anticholeretic effect of somatostatin was not due to the inhibition of endogenous secretin, since cimetidine treatment did not influence the effect of somatostatin on bile flow or bicarbonate secretion. Further, the anticholeretic effect of somatostatin was not vagally mediated, since the infusion of an anticholinergic agent did not alter the effects of somatostatin. It was concluded that, in the dog, the major effect of a pharmacologic dose of somatostatin on bile flow is an anticholeresis caused by either an enhanced ductular reabsorption or inhibition of a ductular secretion of a bicarbonate-rich electrolyte fraction of bile, and that this effect is likely to be mediated by a local effect of somatostatin on the biliary ductule. Thus, in the dog, somatostatin and secretin both evoke ductular modification of bile; however, the effects of the two hormones are exactly opposite to each other.