Anticholeretic effects of substance P and somatostatin.

The aim of the present work was to study the effect of substance P (SP) and somatostatin (SST) on hepatic bile flow. For this purpose a total of 54 anesthetized mongrel dogs were used. The gallbladder was excluded by ligation of the cystic duct and a common duct fistula was created by insertion of a catheter into the common duct. Both SP and SST were found to exert an anticholeretic effect in the dog. SST was also found to be anticholeretic in man. In the dog, SP was infused at dosages from 0.5-20 ng kg-1 min-1 and exerted a significant anticholeretic effect at a dosage of 2.5 ng or higher. At dosages of 2.5 and 20 ng kg-1 min-1, SP decreased the basal bile secretion by about 20 and 40% respectively. The decrease in bile flow was accompanied by decreased outputs of sodium, potassium, chloride, bicarbonate and amylase. With taurocholate-stabilized and taurocholate-stabilized and hormone-induced bile secretion, SP had the above mentioned effects and in addition the output of bile acids decreased. The effect of SP occurred within minutes and after withdrawal of SP there was a positive rebound effect, with a magnitude of about 30% following the 20 ng dosage. SST at dosages from 20-1000 ng kg-1 min-1 induced an anticholeretic effect with a magnitude of 10-25%. With both basal and taurocholate-stabilized bile secretion, the outputs of bile, bile acids and electrolytes decreased during the infusion period and remained diminished for 10-20 min after termination of the infusion. Unlike SP, SST had no anticholeretic effect in the presence of CCK or secretin. A simultaneous infusion of SP and SST decreased bile flow more than either agent alone. The anticholeretic effect of SST was verified in five patients. They had all been operated on for choledocholithiasis. In four patients a complete diversion of bile was obtained with a Foley catheter in the common duct and in the fifth patient from an impacted stone in the common duct. During infusion of SST, 250 ug h-1, the outputs of hepatic bile and bile acids decreased while the outputs of cholesterol and phospholipids were unchanged. The serum bile acid concentration was unaffected by SST and therefore SST is suggested to exert an inhibitory effect on bile acid synthesis. The changes in electrolyte outputs induced by SST in man corresponded to those in the dog.(ABSTRACT TRUNCATED AT 400 WORDS)