G cell

**Location and function:** G cells are neuroendocrine cells in the gastric antrum glands (also in the duodenum, and in small numbers in the pancreas). They secrete gastrin (G17 is the main antral form; G34 is the main duodenal form). Gastrin acts on CCK-B (CCK2) receptors.

**Actions of gastrin:** - Parietal cells: increases H+ secretion directly (Gq, IP3/Ca2+). - ECL cells: stimulates histamine release, which acts on parietal H2 receptors (Gs, cAMP). This is the major route of gastrin's effect. - Trophic effect: promotes growth of gastric mucosa (parietal and ECL cell hyperplasia). - Increases gastric motility.

**Regulation:** - Stimulated by: stomach distention, small peptides and amino acids (especially phenylalanine and tryptophan), vagal stimulation via gastrin-releasing peptide (GRP, bombesin; acts through M3-independent, peptidergic neurons so it is atropine-resistant), and hypercalcemia (calcium and calcium-containing antacids). - Inhibited by: antral pH < 4 (acid acts through somatostatin from D cells, which inhibits G cells by a paracrine effect), and by somatostatin, secretin, GIP, and CCK in other contexts. - Vagal ACh acts mainly on ECL and parietal cells, and also inhibits D cells, which removes inhibition of G cells.

**Clinical correlations:** - **Zollinger-Ellison syndrome (gastrinoma):** An autonomous gastrin-secreting tumor (gastrinoma triangle: pancreas and duodenum). It causes refractory, multiple, or atypical peptic ulcers (e.g., jejunal), diarrhea/steatorrhea (acid inactivates lipase and damages the mucosa), and thick gastric folds. Strongly associated with MEN1 (parathyroid, pituitary, pancreas). Diagnosis: elevated fasting gastrin with low gastric pH (<2); secretin stimulation test shows a paradoxical increase in gastrin (normally secretin decreases it). Treatment is high-dose PPIs and surgical resection. - **Atrophic gastritis (autoimmune, type A):** Loss of parietal cells leads to achlorhydria, which removes negative feedback and causes G cell hyperplasia with high gastrin. Associated with pernicious anemia (loss of intrinsic factor), and an increased risk of gastric carcinoid (ECL cell tumors) and gastric adenocarcinoma. - **PPI use:** Reduced acid leads to hypergastrinemia (rebound acid hypersecretion on stopping). - **H. pylori:** Antral-predominant infection reduces D cell somatostatin, causing increased gastrin and acid, which leads to duodenal ulcers. Pangastritis/body-predominant infection reduces acid and increases gastric cancer risk. - **Antral G cell hyperplasia:** A rare cause of hypergastrinemia. - **Vagotomy/antrectomy:** Antrectomy removes G cells and reduces gastrin.

**Memory aids:** G = Gastrin = Gastric acid. G cells are in the Gastric antrum. D cells (somatostatin) are the brakes. ECL cells (histamine) are the major amplifier. I cells make CCK, S cells make secretin, K cells make GIP, and M cells make motilin.