Stimulation of pepsinogen secretion by the peptic cells in the oxyntic glands occurs in response to two main types of signals: (1) acetylcholine released from the vagus nerves or from the gastric enteric nervous plexus, and (2) acid in the stomach. The acid probably does not stimulate the peptic cells directly but instead elicits additional enteric nervous reflexes that support the original nervous signals to the peptic cells. Therefore, the rate of secretion of pepsinogen, the precursor of the enzyme pepsin that causes protein digestion, is strongly influenced by the amount of acid in the stomach. In people who have lost the ability to secrete normal amounts of acid, secretion of pepsinogen is also decreased, even though the peptic cells may otherwise appear to be normal.
Phases of Gastric Secretion
Gastric secretion is said to occur in three “phases” (as shown in Figure 1): a cephalic phase, a gastric phase, and an intestinal phase.
Fig1. Phases of gastric secretion and their regulation.
Cephalic Phase. The cephalic phase of gastric secretion occurs even before food enters the stomach, especially while it is being eaten. It results from the sight, smell, thought, or taste of food, and the greater the appetite, the more intense is the stimulation. Neurogenic signals that cause the cephalic phase of gastric secretion originate in the cerebral cortex and in the appetite centers of the amygdala and hypothalamus. They are transmitted through the dorsal motor nuclei of the vagi and thence through the vagus nerves to the stomach. This phase of secretion normally accounts for about 30 percent of the gastric secretion associated with eating a meal.
Gastric Phase. Once food enters the stomach, it excites (1) long vagovagal reflexes from the stomach to the brain and back to the stomach, (2) local enteric reflexes, and (3) the gastrin mechanism, all of which cause secretion of gastric juice during several hours while food remains in the stomach. The gastric phase of secretion accounts for about 60 percent of the total gastric secretion associated with eating a meal and therefore accounts for most of the total daily gastric secretion of about 1500 milliliters.
Intestinal Phase. The presence of food in the upper portion of the small intestine, particularly in the duodenum, will continue to cause stomach secretion of small amounts of gastric juice, probably partly because of small amounts of gastrin released by the duodenal mucosa. This secretion accounts for about 10 percent of the acid response to a meal.
Inhibition of Gastric Secretion by Other Intestinal Factors
Although intestinal chyme slightly stimulates gastric secretion during the early intestinal phase of stomach secretion, it paradoxically inhibits gastric secretion at other times. This inhibition results from at least two influences.
1. The presence of food in the small intestine initiates a reverse enterogastric reflex, transmitted through the myenteric nervous system and extrinsic sympathetic and vagus nerves, that inhibits stomach secretion. This reflex can be initiated by (a) distending the small bowel, (b) the presence of acid in the upper intestine, (c) the presence of protein breakdown products, or (d) irritation of the mucosa. This reflex is part of the complex mechanism discussed in Chapter 64 for slowing stomach emptying when the intestines are already filled.
2. The presence of acid, fat, protein breakdown products, hyperosmotic or hypo-osmotic fluids, or any irritating factor in the upper small intestine causes release of several intestinal hormones. One of these hormones is secretin, which is especially important for control of pancreatic secretion. However, secretin opposes stomach secretion. Three other hormones—glucose-dependent insulinotropic peptide (gastric inhibitory peptide), vasoactive intestinal polypeptide, and somatostatin—also have slight to moderate effects in inhibiting gastric secretion.
The purpose of intestinal factors that inhibit gastric secretion is presumably to slow passage of chyme from the stomach when the small intestine is already filled or already overactive. In fact, the enterogastric inhibitory reflexes plus inhibitory hormones usually also reduce stomach motility at the same time that they reduce gastric secretion, as was discussed in Chapter 64.
Gastric Secretion During the Interdigestive Period. The stomach secretes a few milliliters of gastric juice each hour during the “interdigestive period,” when little or no digestion is occurring anywhere in the gut. The secretion that does occur is usually almost entirely of the nonoxyntic type, composed mainly of mucus but little pepsin and almost no acid.
Emotional stimuli may increase interdigestive gastric secretion (which is highly peptic and acidic) to 50 milliliters or more per hour, in much the same way that the cephalic phase of gastric secretion excites secretion at the onset of a meal. This increase of secretion in response to emotional stimuli is believed to contribute to the development of peptic ulcers, as discussed in Chapter 67.
Chemical Composition of Gastrin and Other Gastrointestinal Hormones
Gastrin, cholecystokinin (CCK), and secretin are all large polypeptides with approximate molecular weights of 2000, 4200, and 3400, respectively. The terminal five amino acids in the gastrin and CCK molecular chains are the same. The functional activity of gastrin resides in the terminal four amino acids, and the activity for CCK resides in the terminal eight amino acids. All the amino acids in the secretin molecule are essential.
A synthetic gastrin, composed of the terminal four amino acids of natural gastrin plus the amino acid alanine, has all the same physiological properties as the natural gastrin. This synthetic product is called pentagastrin.
