Effect of cholestyramine on plasma cholecystokinin and pancreatic polypeptide levels, and exocrine pancreatic secretion

Abstract

Abstract. The effect of acute and long-term administration of cholestyramine, a non-absorbable bile salt binding resin, on exocrine pancreatic secretion, plasma-cholecystokinin (CCK) and plasma-pancreatic polypeptide (PP) was investigated in 10 healthy volunteers. Oral ingestion of 12 g cholestyramine augmented the stimulatory effect of a liquid test meal on plasma-CCK (3.5-fold) and plasma-PP (2-fold). During prolonged treatment with 3 x 12 g cholestyramine daily for 4 weeks, the most pronounced increase in basal hormone levels was observed after 1 day, but progressively decreased during treatment and had normalized after 4 weeks. However, the stimulated plasma-CCK output was still significantly elevated after cessation of treatment, compared with pretreatment values. After acute and chronic cholestyramine administration only stimulated lipase secretion was elevated, whereas trypsin and amylase remained unchanged. It is suggested that removal of bile salts enhances CCK and thereby PP release and pancreatic lipase secretion.

Lack of effect of the specific cholecystokinin receptor antagonist loxiglumide on cholecystokinin clearance from plasma in man.

“…This study further supports the existence of a negative feedback mechanism between plasma CCK and bile products in the lumen of the proximal small intestine (Adler et al, 1988;Gomez et al, 1988;Koop et al, 1988Koop et al, , 1989. However, other mechanisms of an augmented stimulated CCK release during loxiglumide administration, such as direct effects of loxiglumide on CCK-producing cells or indirect effects via yet to be established paracrine, neurocrine or endocrine mechanisms cannot be excluded.…”

“…Furthermore, gallbladder contraction in response to these stimuli was virtually abolished by loxiglumide (Douglas et al, 1989;Meyer et al, 1989), supporting an important role for the gallbladder in a negative feedback mechanism between bile-products in the lumen of the proximal small intestine and CCK-release (Gomez et al, 1988;Koop et al, 1988Koop et al, , 1989.…”

Protective action of luminal bile salts in necrotizing acute pancreatitis in mice.

“…Therefore, it seems that the act of a stone passing through the ampulla of Vater would invariably be accompanied by a significant reduction in the amount of bile salts into the duodenum. Recent studies in normal volunteers by Koop et al (31) have shown that removal of bile salts with cholestyramine enhances both the release of CCK and pancreatic exocrine secretion stimulated by a liquid test meal.…”

Cholestyramine Influences Meal-Stimulated Pancreaticobiliary Function and Plasma Cholecystokinin Independent of Gastric Emptying and Food Digestion

“…Cholestyramine is a drug used in clinical practice to lower plasma cholesterol levels, to treat obstructive liver diseases, or to decrease diarrhoea induced by bile salt overflow into the colon. Recently, cholestyramine has also been used as a tool in physiologic studies to investigate the role of bile salts in the regulation of plasma cholecystokinin (CCK) release and pancreaticobiliary secretion (1)(2)(3)(4)(5).…”