Neurohormonal Control of Human Pancreatic Exocrine Secretion

Abstract

Near the end of the last century, Pavlov suggested that pancreatic secretion was exclusively controlled by neural reflex mechanisms (1). In 1902, Bayliss and Starling published their results on secretin, opening the field of gastrointestinal endocrinology while arguing that neural regulation of the pancreas is "superfluous and improbable" (2). In the following decades, especially after the discovery of cholecystokinin (CCK), it was generally held that exocrine pancreatic secretion is mainly regulated by hormones. Thus, investigators have historically tended to adopt an "all-or-nothing" approach; current appreciation of the complexity of mechanisms governing most biologic phenomena leads us to accept that the pancreas is regulated through an interplay of multiple neural and hormonal pathways.Several factors have impeded conclusive definition of the relative contribution of neural and hormonal control of pancreatic secretion. First, the information accumulated over the last several years clearly indicates that results obtained in one species cannot be directly transferred to another. Second, many conclusions were based on infusion of regulatory peptides at supraphysiologic concentrations, which may not accurately reveal their physiologic role. Sensitive and specific assays detecting postprandial plasma levels have now been established for most relevant substances. Third, even infusion of peptides at postprandial plasma levels may not fully elucidate their role as physiologic mediators.Plasma levels obtained from peripheral veins do not necessarily reflect concentrations at the pancreatic receptor, and exogenous infusion may not accurately mimic endogenous release. Fourth, selective receptor antagonists for the peptides in question have only recently become available. The application of effective receptor blockers (e.g., pentanoic acid and benzodiazepine derivatives for CCK receptors) has greatly aided our understanding of physiologic roles. Fifth, pancreatic function is regulated not only by peptide hormones from gastrointestinal endocrine cells, but also by regulatory peptides localized in pancreatic nerve fibers. Finally, pancreatic function is integrated through a complex interaction of mucosal, humoral, neural, and myogenic factors that regulate gastrointestinal secretion and motility. Analysis of a single factor allows only a limited view of pancreatic function as an integral component of the gastroenteropancreatic system.In this review, we have attempted to bring together findings from our groups and others, in order to provide an integrative concept of the neurohormonal systems controlling human exocrine pancreatic secretion. This overview evolved from the first Frank Pickering Brooks Basic Science Lecture, given by the first author at the American Pancreatic Association in 1992. For further review of the regulation of pancreatic exocrine secretion in man and other species, we also refer the reader to several excellent reviews published recently (3-7). EFFECTS OF EXOGENOUS ADMINISTRATION OF SECRETAGOGUESIntr...

Differential expression of the CCK-A and CCK-B/gastrin receptor genes in human cancers of the esophagus, stomach and colon

“…The RT-PCR method was first validated by measuring mRNA levels in normal human tissues known or expected to contain CCK-A-and/or CCK-B/gastrin receptors. The distribution of CCK-A-and CCK-B/gastrin-receptor mRNA found by our RT-PCR method agrees with results from studies that used other methods, including Northern blotting, radioligand binding, and functional studies (Adler et al, 1995;Dietl and Palacios, 1989;Ito et al, 1993;Lloyd and Debas, 1994;Monstein et al, 1996;Schjoldager et al, 1989). Importantly, we obtained a quantitative distribution of the 2 receptor transcripts in several human tissues.…”

Acute pancreatitis possible initial triggering mechanism and prophylaxis

“…This process worsens as it associates with an altered enteropancreatic feedback, due to the absence of bilio-pancreatic secretion in the duodenal lumen. This gives rise to an increased CCK blood level activating pancreonal stimulation by a hormonal mechanism through the blood stream and a neural mechanism that involves paracrine action on afferent nerve fibers of the autonomous nervous system on the duodenal wall [49,50].…”

Development and regulation of pancreatic juice secretion in cattle. State-of-the-art

“…Moreover, a similar cephalic phase was observed after giving an empty feeding-bucket to the calf to suckle for couple of minutes (Lesniewska and Zabielski, unpublished data). Intraduodenal administration of CCK-A receptor antago- nist lowered the protein output during the cephalic phase suggesting that, unlike in humans, a CCK component was involved in this response (Addler et al, 1995). The cephalic phase of pancreatic secretion was present only in the suckling calves fed liquid feed (milk or milk replacer), and was much more evident following the morning feeding than the evening one (Zabielski et al, 1997).…”

“…The vagal nerves appear to play a more important role in the regulation of exocrine pancreatic secretion in preruminant calves than in dogs. In calves, the vagal and cholinergic pathways appear to dominate all the regulatory mechanisms of pancreatic juice secretion and there are many similarities to the mechanisms found in humans (Addler et al, 1995). Vagi are responsible for the generation of the periodic pancreatic activity in calves since atropine and 4-DAMP can completely block this activity, and cold vagal blockade can almost completely block the periodic pancreatic fluctuations (Zabielski and Naruse, 1999).…”