Secretion from acinar cells of the exocrine pancreas: Role of enteropancreatic reflexes and cholecystokinin

Abstract

Although the molecular machinery and mechanism of cell secretion in acinar cells of the exocrine pancreas is well documented and clear, only recently has the pharmacophysiology of pancreatic exocrine secretion come to light. Therefore, we focus in this article on the current understanding of the pharmacophysiology of pancreatic exocrine secretion. The pancreatic secretory response to ingestion of a meal is mediated via a complex interplay of neural, humoral and paracrine mediators. A major role in the control of the intestinal phase of pancreatic secretion is attributed to vago-vagal enteropancreatic reflexes. In the scheme of this control mechanism, afferents originating in the duodenal mucosa, and efferents mediating central input on the pancreatic ganglia, activate intrapancreatic postganglionic neurons. Experiments utilizing specific receptor antagonists demonstrate the involvement of both muscarinic M1 and M3 receptors expressed in pancreatic acinar cells. Cholecystokinin (CCK), originally implicated in the humoral secretion of pancreatic enzymes, through a direct action on acinar CCK receptors, is also essential to the enteropancreatic reflex mechanism. CCK stimulation of the exocrine pancreatic secretion through excitation of sensory afferents of the enteropancreatic reflexes, is a paracrine mode of CCK action, and is probably the only one in humans and the predominant one in rats. In dogs, however, CCK acts on the pancreas via both the humoral and a paracrine route. More recent experiments suggest further possible sites of CCK action. Additionally, at the brain stem, vago-vagal enteropancreatic reflexes may be modulated by input from higher brain centres, particularly the hypothalamic-cholinergic system in the tonic stimulation of preganglionic neurons of the dorsal motor nucleus of the vagus projecting into the pancreas.

Cellular and subcellular localization of cholecystokinin (CCK)-1 receptors in the pancreas, gallbladder, and stomach of mice

“…Besides the direct stimulation by CCK, indirect pathways via the vagal nerve have been proposed for the regulation of the pancreas and gallbladder (Mawe 1991;Owyang and Logsdon 2004;Singer and Niebergall-Roth 2009). CCK also plays a role in the intestinal phase in the control of gastric functions that negatively regulate meal-stimulated gastric acid secretion and gastrin release (Lloyd et al 1992a, b), possibly via somatostatin release (Schmidt et al 1994).…”

New Advances in Cell Physiology and Pathophysiology of the Exocrine Pancreas

“…The vagus mediates a small cephalic phase. Vagal afferents and vagal-vagal reflexes do play a role [4]. Pancreatic acinar cells have M1 and M3 receptors and there is probably some direct innervation of the pancreas from the gut.…”

Disruption of Cell Cycle Machinery in Pancreatic Cancer

“…MUC1) occurs in many different types of cancers, including pancreatic (Moniaux, et al, 2004). Based on their unique genetic background, centroacinar cells have been implicated as the potential cell of origin giving rise to ductal adenocarcinomas (Singer & Niebergall-Roth, 2009, Stanger & Dor, 2006. Digestive pro-enzymes for breaking down fats and protein are secreted into the lumen of the acinus by basophilic cells, so-called because they tend to stain intensely with basic dyes (Singer & Niebergall-Roth, 2009).…”

“…Based on their unique genetic background, centroacinar cells have been implicated as the potential cell of origin giving rise to ductal adenocarcinomas (Singer & Niebergall-Roth, 2009, Stanger & Dor, 2006. Digestive pro-enzymes for breaking down fats and protein are secreted into the lumen of the acinus by basophilic cells, so-called because they tend to stain intensely with basic dyes (Singer & Niebergall-Roth, 2009). These cells contain large cytoplasmic secretory granules in which digestive pro-enzymes are maintained in an inactive state, a method of regulatory control that is essential to prevent auto-degradation of the cell and subsequent development of a condition called acute pancreatitis (Waldthaler, et al, 2010).…”