review of literature on clinical pancreatology - The Pancreapedia

PANCREATIC PHYSIOLOGYSphincter <strong>of</strong> OddiThe most common functional disorder <strong>of</strong> the biliary tract and pancreas relates to the activity<strong>of</strong> the Sphincter <strong>of</strong> Oddi. The Sphincter <strong>of</strong> Oddi is a small smooth muscle sphincterstrategically placed at the junction <strong>of</strong> the bile duct, pancreatic duct, and duodenum. Thesphincter controls flow <strong>of</strong> bile and pancreatic juices into the duodenum and prevents reflux <strong>of</strong>duodenal content into the ducts. Disorder in its motility is called Sphincter <strong>of</strong> Oddidysfunction. Clinically this presents either with recurrent abdominal biliary type pain orepisodes <strong>of</strong> recurrent pancreatitis. Manometry may identify the motility abnormalities, themost clinically significant being an abnormally elevated basal pressure. The most effectivetreatment once an abnormal basal pressure is identified is division <strong>of</strong> the sphincter. This isassociated with good long-term results [126].Modulatory drugs <strong>of</strong> gastrointestinal (GI) motility are a possibility for use to relieve the mainclinical presentation <strong>of</strong> sphincter <strong>of</strong> Oddi (SO) dysfunctions which are not easily distinguishedfrom those occurring in high prevalence functional GI disorders. The aim <strong>of</strong> one study was toinvestigate the effects <strong>of</strong> GI motility modulators including pinaverium, domperidone,trimebutine, and tegaserod on the contractile activity <strong>of</strong> SO stimulated by carbachol in therabbit. The contraction responses precontracted by carbachol (0.1 µM) <strong>of</strong> in vitro rabbit SOrings were evaluated before and after the addition <strong>of</strong> a series concentration (10 -13 to 10 -3 M) <strong>of</strong>pinaverium, domperidone, trimebutine, and tegaserod. Pinaverium induced a concentrationdependentrelaxation <strong>of</strong> isolated SO rings precontracted with carbachol (0.1 µM). Tegaseroddid not significantly effect SO motility, but domperidone seemed to stimulate SOcontractions. At low doses (10 -13 to 10 -7 M), trimebutine stimulated SO contraction; however,high doses (10 -6 to 10 -3 M) <strong>of</strong> trimebutine inhibited SO motility. It was concluded thatpinaverium totally inhibits contractions induced by carbachol and tegaserod has no effect oncarbachol-induced contractions. Domperidone stimulates contractions induced by carbachol.Trimebutine could either stimulate or inhibit SO contractions depending on its dosage [127].FeedingThe complex control <strong>of</strong> food intake and energy metabolism in mammals relies on the ability<strong>of</strong> the brain to integrate multiple signals indicating the nutritional state and the energy level <strong>of</strong>the organism and to produce appropriate responses in terms <strong>of</strong> food intake, energyexpenditure, and metabolic activity. Central regulation <strong>of</strong> feeding is organized as a long-loopmechanism involving humoral signals and afferent neuronal pathways to the brain,processing in hypothalamic neuronal circuits, and descending commands using vagal andspinal neurons. Sensor mechanisms or receptors sensitive to glucose and fatty acidmetabolism, neuropeptide and cannabinoid receptors, as well as neurotransmitters andneuromodulators synthesized and secreted within the brain itself are all signals integrated inthe hypothalamus, which therefore functions as an integrator <strong>of</strong> signals from central andperipheral structures. Homeostatic feedback mechanisms involving afferent neuroendocrineinputs from peripheral organs, like adipose tissue, gut, stomach, endocrine pancreas,adrenal, muscle, and liver, to hypothalamic sites thus contribute to the maintenance <strong>of</strong>normal feeding behavior and energy balance. In addition to transcriptional events, peripheralhormones may also alter firing and/or connection (synaptology) <strong>of</strong> hypothalamic neuronalnetworks in order to modulate food intake. Moreover, intracellular energy sensing andsubsequent biochemical adaptations, including an increase in AMP-activated protein kinaseactivity, occur in hypothalamic neurons. Understanding the regulation <strong>of</strong> appetite is clearly amajor research effort but also seems promising for the development <strong>of</strong> novel therapeuticstrategies for obesity [128].