Postprandial control of gallbladder contraction and exocrine pancreatic secretion in man

Abstract

To explore the interactions between cholecystokinin (CCK) and the cholinergic system, we compared the effect of cholinergic or peptidergic CCK blockade on gallbladder contraction and pancreatic enzyme secretion using atropine and loxiglumide (a specific CCK antagonist) as pharmacological tools. Gallbladder contraction was measured by sonography and pancreatic secretion by a marker perfusion and aspiration technique. Graded doses of exogenous CCK8 induced dose-dependent contractions of the gallbladder and increasing enzyme outputs. Loxiglumide (10 mg kg-1 h-1) abolished the gallbladder response and prevented an increase in pancreatic enzyme secretion to CCK8. Atropine (5 micrograms kg-1 h-1), however, only reduced gallbladder contraction and enzyme output to CCK8. Gallbladder volumes decreased maximally to 12 +/- 4% after oral food, whereas enzyme output and plasma CCK levels increased 6- to 8-fold. Loxiglumide completely abolished gallbladder contraction and inhibited enzyme secretion by 30%. Atropine caused a small reduction in gallbladder volumes, but essentially blocked postprandial enzyme secretion. The results indicate that CCK is the major regulator of gallbladder contraction with the cholinergic system modulating the response, while the exocrine pancreas is crucially dependent on a cholinergic background with CCK modulating the secretory response.

How does cholecystokinin stimulate exocrine pancreatic secretion? From birds, rodents, to humans

“…In another study, trypsin output stimulated by physiological doses of CCK was inhibited by atropine by 84.0%, whereas lipase output was inhibited by 78.6% in humans (132). Thus the human exocrine pancreas is crucially dependent on a cholinergic background, with CCK only modulating this secretory response (9).…”

“…Atropine blocked significantly meal-stimulated pancreatic digestive enzyme secretion, and the response to graded doses of exogenous CCK was significantly inhibited by both atropine and loxiglumide, a CCK1R antagonist, suggesting that pancreatic enzyme secretion is predominantly dependent on a cholinergic tone and that CCK modulates the enzymesecretory response in human (1). Atropine (5 g ⅐ kg Ϫ1 ⅐ h Ϫ1 ) reduced the CCK-stimulated increase in pancreatic enzyme secretion and essentially blocked postprandial enzyme secretion (9). In another study, trypsin output stimulated by physiological doses of CCK was inhibited by atropine by 84.0%, whereas lipase output was inhibited by 78.6% in humans (132).…”

Pharmacological profile of TP‐680, a new cholecystokininA receptor antagonist

“…Adrian, 1995). A number of clinical studies with another CCK receptor antagonist, loxiglumide, suggested that CCK is involved in postprandial pancreatic enzyme secretion (Meyer et al, 1989;Hildebrand et al, 1990;Beglinger et al, 1992a), whereas MK-329 failed to inhibit postprandial pancreatic trypsin output (Cantor et al, 1992). Furthermore, loxiglumide significantly accelerates gastric emptying of test meal in human subjects (Meyer et al, 1989;Fried et al, 1991), whereas MK-329 has little effect on postprandial gastric emptying in man (Liddle et al, 1989;Cantor et al, 1992).…”

“…However, further studies using other CCKA receptor antagonists may be helpful in elucidating the physiological role of CCK. Thus, the development of CCKA receptor antagonists with higher selectivity for CCKA versus CCKB receptors or -with different characteristics is desirable in order to investigate new insights into digestive physiology and pathophysiology, to distinguish further CCK receptor substypes, and to examine the role of CCK in the treatment of gastrointestinal disorders (Meyer et al, 1989;Beglinger et al, 1991;1992a;Rovati, 1991;Schmidt et al, 1991;Niederau et al, 1992;Tani et al, 1993;Herrington & Adrian, 1995).…”

Role of Free Fatty Acids in Regulating Gastric Emptying and Gallbladder Contraction

“…Experimental evidence suggests that different macronutrients act via different mechanisms. Along this line, the small intestine plays a role in inhibiting gastric emptying [1, 3], in stimulating gallbladder contraction and exocrine pancreatic secretion [4, 5], and finally in inhibiting food intake in response to intraduodenal (ID) lipid [6, 7]. To further the understanding of the transduction mechanisms, it is important to consider the pathways of fat digestion.…”