Differential mechanism and site of action of CCK on the pancreatic secretion and growth in rats

Abstract

Recent studies demonstrated that cholecystokinin (CCK) at physiological levels stimulates pancreatic enzyme secretion via a capsaicin-sensitive afferent vagal pathway. This study examined whether chemical ablation of afferent vagal fibers influences pancreatic growth and secretion in rats. Bilateral subdiaphragmatic vagal trunks were exposed, and capsaicin solution was applied. Pancreatic wet weight and pancreatic secretion and growth in response to endogenous and exogenous CCK were examined 7 days after capsaicin treatment. Perivagal application of capsaicin increased plasma CCK levels and significantly increased pancreatic wet weight compared with those in the control rats. Oral administration of CCK-1 receptor antagonist loxiglumide prevented the increase in pancreatic wet weight after capsaicin treatment. In addition, continuous intraduodenal infusion of trypsin prevented the increase in plasma CCK levels and pancreatic wet weight after capsaicin treatment. There were no significant differences in the expression levels of CCK-1 receptor mRNA and protein in the pancreas in capsaicin-treated and control rats. Intraduodenal administration of camostat or intravenous infusion of CCK-8 stimulated pancreatic secretion in control rats but not in capsaicin-treated rats. In contrast, repeated oral administrations of camostat or intraperitoneal injections of CCK-8 significantly increased pancreatic wet weight in both capsaicin-treated and control rats. Present results suggest that perivagal application of capsaicin stimulates pancreatic growth via an increase in endogenous CCK and that exogenous and endogenous CCK stimulate pancreatic growth not via vagal afferent fibers but directly in rats.

Cholecystokinin and Gastrin Receptors

“…The neural circuitries involving CCK1R of capsaicin-sensitive vagal afferent neurons, central synapses, and vagal cholinergic efferent fibers (represented in Fig. 6) were recently confirmed by Yamamoto et al (580). Although most of the information on the vagal CCK1R is obtained from research in animals, observations were reported in humans suggesting that CCK stimulates the pancreas via a pathway dependent on cholinergic innervation (35, 493).…”

Calcineurin mediates pancreatic growth in protease inhibitor-treated mice

“…Although camostat feeding may also increase the release of endogenous secretin (49), it is clear that it is CCK that is required for camostat-induced growth. The trophic effect of CCK in rats appears primarily to be through high-affinity CCK receptors (7) located on the acinar cells (53). The effect of the high-protein diet may be mediated by another hormone or neural pathway but also may be mediated by amino acids from the dietary protein.…”

Control of gallbladder contractions by cholecystokinin through cholecystokinin-A receptors on gallbladder interstitial cells of cajal

“…It is well established that CCK-AR and CCK-BR regulate a number of physiological functions, e.g. gallbladder contraction [6] , pancreatic enzyme release [7] , gastric acid secretion [8] and pyloric sphincter closure [9,10] . In 1892, a special kind of cell which is now called "interstitial cells of Cajal" (ICC) in the gastrointestinal tract was first described by the famous Spanish neuro-histologist Ramony Cajal [11] .…”