Where is the primary site of action of CCK for initiating sphincter of Oddi relaxation?

Abstract

The delivery of bile into the duodenum is controlled by the motor activity of the gallbladder and sphincter of Oddi (SO). 1 In humans and dogs, the SO acts as a resistor to the outflow of bile. During the interdigestive period, when there is no duodenal activity, the basal pressure and rhythmic contractions of the SO exceed the hepatic secretory pressure of bile, which results in the gradual filling of the gallbladder. Ingestion of a meal induces gallbladder contraction and relaxation of the SO via the release of cholecystokinin (CCK) and the vagal reflex. The gallbladder pressure is higher than the intraduodenal pressure, which allows entry of bile into the duodenum and prevents the regurgitation of the duodenal contents back into the biliary tract. In the fasting state, bile is cyclically secreted into the duodenum by periodic contractions of the gallbladder associated with the migrating motor complex (MMC) of the duodenum. 2 The gallbladder contraction occurs at the beginning of the phase-II contraction of the duodenum, 3 which is dependent on intact vagal innervation. 4 During phases II and III, when the duodenal pressure exceeds 100 mmHg, the contractions of the SO are coordinated in phase with those of the duodenum to prevent regurgitation. The SO and the duodenum act independently, but their functions are coordinated for the optimal duodenal delivery of bile. However, it is not known exactly how their coordination is controlled.Many physiological and anatomical studies 5 indicate the existence of neuronal connections between the duodenum and the biliary tract (the gallbladder and SO). The neurons of the SO are regulated by the parasympathetic (vagus) and sympathetic nerves, and by gut hormones, such as CCK. In addition, there is an intramural neural projection to the SO ganglia from the myenteric plexus of the duodenum in the Australian possum and guinea pig. 6,7 Physiological concentrations of CCK-around 5 pM following meal ingestion 8 -stimulate contractions of the gallbladder, where the smooth muscle cells express CCK-A (CCK1) receptors. 9 In humans and dogs, in which the SO acts as a resistor, CCK causes relaxation; it decreases the SO basal pressure and abolishes its phasic contractions. The relaxation appears to be mediated by neural mechanisms, as tetrodotoxin inhibits the relaxation evoked by CCK. 10 The candidates for inhibitory mediators are vasoactive intestinal peptide (VIP) and nitric oxide (NO). The stimulatory effect of CCK after the application of tetrodotoxin is probably a direct effect of CCK on the SO. Exogenous CCK elicits a paradoxical response (contraction) of the SO in some patients with biliary dyskinesia and in some patients who have undergone surgery of the upper gastrointestinal tract.In this issue of the Journal of Gastroenterology, Dong et al. 11 report their investigation of how surgical separation of the SO from the duodenum affected the SO response to CCK octapeptide (CCK-8). They found that an intravenous injection of CCK-8 failed to elicit SO inhibition in duodenectomized ...

Neurohormonal regulation of the sphincter of oddi

“…Importantly, the authors propose that the paradoxical response to CCK observed in patients with SO dysfunction is not mediated by CCK receptors on the smooth muscle but instead may be mediated by a mechanism requiring duodenal myoneural continuity. However, the site of action of CCK for initiating SO relaxation is still debated [18]. In contrast to the previously described study, Naruse [18] hypothesizes, on the basis of numerous surgical models, that CCK probably induces SO relaxation via activation of extrinsic nerves.…”

“…However, the site of action of CCK for initiating SO relaxation is still debated [18]. In contrast to the previously described study, Naruse [18] hypothesizes, on the basis of numerous surgical models, that CCK probably induces SO relaxation via activation of extrinsic nerves. He suggests that further studies should consider a broader range of CCK concentrations, along with the role of ICC, neural connections among the SO, gallbladder/common bile duct, and stomach, and whether CCK-A receptors are located on vagal afferent nerve fibers in the duodenum.…”

Bi-directional regulation of acupuncture on extrahepatic biliary system: An approach in guinea pigs

“…It indicates that acupuncture at CO11 can partially block the inhibitory effect of atropine on SO EMG. Though the exact pathway for this effect remains unclear, it may be partially attributed to the secretion of cholecystokinin (CCK) as an important ghrelin that has an excitatory effect on the SO EMG 27 .…”