Insulin Receptor - Related Receptor Messenger Ribonucleic Acid Levels Are up - Regulated in Enterochromaffin - like Cell Pathophysiology

Insulin Receptor-related Receptor Messenger Ribonucleic Acid Levels are Upregulated in Enterochromaffin-like Ce11 Pathophysiology. Lisa Anne Ilk. Master of Science, 1 999. Department of Physiology. University of Toronto. The insulin receptor-related receptor (IRR). an orphan member of the insulin receptor family. is selectively localized in the stomach to a subset of neuroendocrine cells. the enterochrornanin-like (ECL) cells. ECL cells are the pivotal regulators of gastric acid secretion. The physiological role of IRR was investigated by analyzing its mRNA levels using semi-quantitative RT-PCR in two States of ECL ce11 pathophysiology in the rat. First. hyperpastrinemia which stimulates ECL ce11 activity and replication was induced by gastric gavage of omepnzole which blocks acid release. Second. a hypogastrinemic state in which ECL ce11 activity was reduced was achieved by fasting. As expected. mRNA levels of the ECL ce11 markers histidine decarboxylase and gastrin receptor increased in hypeqastrinemia and decreased with fasting. IRR mRNA levels also were shown to parallel ihe increase in ECL cell activity in hypergastrinemia. In fasting, however, like the insulin and IGF-1 receptors. IRR mRNA levels increased despite the decrease in ECL ce11 activity. Since IRR mRNA levels were not exclusively conditional on ECL cell activity, they may represent a response to the decreased acid secretion or responses more specific to hypergastrinemia and fasting, for example to increased ECL ce11 activity and loss of ligand, respectively.