Human Biochemistry, Volume 2 - Murray R. 1993

Biochemistry of Intracellular and Intercellular Communication
Gastrointestinal Hormones
Gastrin-Cholecystokinin Family

Gastrin is produced by G Cells located in the mucosa of the gastric antrum and, to a lesser extent, the duodenal mucosa. It exhibits greater heterogeneity in molecular size and number of forms than any other gastrointestinal hormone (Table 52.4). Furthermore, each form of gastrin exists in both sulfated and unsulfated states (at a single Tyrosine residue; Table 52.5). The C-terminal 14 Amino Acids are identical in gastrin 34, gastrin 17, and gastrin 14. Gastrin 34 is present in the Blood in higher amounts than gastrin 17, likely because its plasma half-life (15 min) is 5 to 7 times longer than that of gastrin 17. The latter appears to act as the primary stimulator of gastric acid secretion, which is regulated by a negative feedback mechanism, as acidification of the antral contents suppresses gastrin secretion. Gastrin also stimulates Pepsin secretion and causes gastric mucosal hypertrophy. Biological activity resides in the C-terminus of the hormone; the C-terminal pentapeptide elicits the full spectrum of Physiological effects of gastrin 17, yet possesses only 1/10th of its biological activity on a mass basis.

Homology between gastrin and cholecystokinin is particularly pronounced in their C-terminal regions: the last 5 amino acids of both molecules are identical (Table 52.5). Both Peptides contain a sulfated tyrosine residue, but this residue is non-essential for gastrin activity (stimulation of gastric acid and pepsin secretion), whereas maximum cholecystokinin activity (stimulation of pancreatic enzyme secretion and Gallbladder contraction) requires a 7-amino-acid C-terminal fragment containing a sulfated tyrosine.

Gastrin-secreting tumors (gastrinomas) are associated with excessive gastric acid production and The Development of refractory peptic ulcers. The C-terminal pentapeptide (pentagastrin) stimulates Calcitonin secretion and is used in provocative testing for medullary thyroid carcinoma.

Cholecystokinin (CCK) exists in at least 5 molecular forms (Table 52.4), of which CCK-8 is the most abundant in blood and the most active. Cholecystokinin is synthesized by I cells in the mucosa of the duodenum and proximal jejunum and is secreted in response to peptides, amino acids, long-chain Fatty acids, calcium, and acid. Its physiological effect is to stimulate gallbladder contraction and pancreatic enzyme secretion. Like all Other Gastrointestinal Peptides, it exhibits numerous additional activities, the most enigmatic of which is its ability to induce satiety (CCK-8 has also been detected in the Brain).