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Wikipedia / Acinar cell

Acinar cells are the primary digestive enzyme secreting cells of the pancreas. Together with the bicarbonate-producing ductal cells, they are one of the main types of exocrine cell found in the pancreas. Acinar cells are located around special cavities called acini (meaning: “berry in a cluster”) which is the origin of their name.

Function

Acinar cells synthesize digestive enzymes, which they store in small cellular compartments called granules. These enzymes are released when the cells are stimulated by particular hormones (like CCK) or neurotransmitters (like acetylcholine), where they combine with water and ions to form pancreatic juice, which eventually flows into the first part of the intestines (the duodenum). In the duodenum, the enzymes in the pancreatic juice break down food molecules such as proteins and fats, allowing them to eventually be absorbed by the small intestines.

Major secreted enzymes

Proenzymes

Certain enzymes could damage the pancreas if they were allowed to act on pancreatic cells, so instead they are kept in an inactive form. These inactive enzymes are called proenzymess. In particular, this is done for enzymes that break down proteins and peptides (proteases) and enzymes that break down phospholipids (phospholipases) which are a major component of cell membranes.

After reaching the intestines, the intestinal enzyme enteropeptidase activates some of the proenzyme trypsinogen into active trypsin. The newly activated trypsin (and other pancreas enzymes like chymotrypsin-C) then activate the other proenzymes, including any remaining trypsinogen.

Note: the names of proenzymes are typically distinguished from their active form by adding a “pro-” prefix, or an “-ogen” suffix, so for example, trypsinogen is the inactive proenzyme for trypsin.

Active enzymes

Other enzymes are stored in active form, probably because they are unlikely to encounter their target molecules in the pancreas.

Coenzymes and activators

  • Colipase — protein that binds to pancreatic lipase and helps it function more efficiently.

  • Chymotrypsin-C — Protease that works together with trypsin to activate procarboxypeptidases A1 and A2.

Stimulation of enzyme secretion

A large number of hormones and neurotransmitters have been implicated in regulating the secretion of digestive enzymes from acinar cells, and these have different impacts at different phases of digestion.

Nervous system stimulation

First, anticipation of food driven by the senses (including sight, smell, and taste) triggers the release of digestive enzymes. This appears to be driven by the unconscious nervous system. In particular, the vagus nerve directly signals to acinar cells using neurotransmitters, especially acetylcholine.

Next, after food enters and stretches the stomach, this triggers additional signaling from the vagus nerve, similarly leading to enzyme secretion.

While acetylcholine appears to have a central role in these processes, many other neurotransmitters appear to also play a part, including Gastrin-releasing peptide, Substance P, and vasoactive intestinal peptide.

Hormonal stimulation

After food reaches the start of the intestines (the duodenum), proteins and fats trigger intestinal I cells to release the hormone cholecystokinin (CCK), while gastric acid triggers S cells to release secretin. These each stimulate the pancreas to release pancreatic juice in a different way, and together with the additional neuronal stimulation during this phase account for 50-80% of total pancreatic secretion.

In the pancreas, CCK primarily stimulates acinar cells to release enzymes, while secretin primarily stimulates ductal cells to release bicarbonate. Nevertheless, this is not a hard distinction, and secretin also directly stimulates acinar cells.

CCK and secretin are the primary hormones regulating this intestinal phase, but other hormones are also involved in the regulation of digestive enzyme release, including insulin.

Receptors

In acinar cells, most of the main secretion regulating hormones/neurotransmitters bind to a type of membrane receptor called G protein-coupled receptors. Notably, CCK binds to the cholecystokinin A receptor, while acetylcholine binds to the muscarinic acetylcholine receptors CHRM1 and CHRM3, with CHRM3 probably being the primary one given its greater expression in acinar cells.

More generally the G-coupled receptors tend to fall into two groups. The CCK, Acetylcholine, Gastric-releasing peptide, and Substance P receptors are linked to Gq alpha subunit family G-proteins, while the secretin and vasoactive intestinal peptide receptors are linked to Gs alpha subunit family G-proteins. These act synergistic, with activation of receptors from both families leading to greater secretion than the sum of the parts.

Clinical significance

Damage to acinar cells is the characteristic cause of acute pancreatitis. This damage leads to an inappropriate release and activation of trypsin (and subsequently other digestive enzymes) into the pancreas, causing further acinar cell damage, and potentially death. Acute pancreatitis is one of the most common gastrointestinal conditions that leads to hospitalization. Gallstones and alcohol are the two most common causes of acute pancreatitis.

Acinar cell carcinoma (ACC) is a rare type of pancreatic cancer originating in acinar cells, accounting for around 1-2% of adult pancreatic cancers, and about 15% of pediatric pancreatic cancers. Distinct from other types of pancreatic cancer, ACC may lead to excessive lipase secretion (lipase hypersecretion syndrome), which can cause the death of fat tissue in the skin and bone (fat necrosis), but this doesn’t happen in all affected people.

Other notable proteins

Aside from the major enzymes and coenzymes, there are a number of other genes/proteins with particular specificity to acinar cells:

Secreted proteins

Other zymogen granule proteins

  • Synocollin (SYCN) — protein predicted to be involved in the regulation of acinar cell secretion, and in particular the fusion of zymogen granules.

    CUB and ZP domain-containing protein 1 (CUZD1) — zymogen granule protein that is predicted to be involved in trypsinogen activation.

Transcription factors

  • Pancreas-specific transcription factor 1a (PTF1A) — transcription factor involved in determining which cells become part of the pancreas instead of the duodenum during development, and may also be involved in maintaining the specific gene expression of the exocrine pancreas.

    Transcription factor RBP-L (RBPJL) — putative transcription factor and paralog of RBPJ that may interact with EBNA2.

See also

References