Ischemia of rat stomach mobilizes ECL cell histamine

Abstract

Microdialysis was used to study how ischemia-evoked gastric mucosal injury affects rat stomach histamine, which resides in enterochromaffin-like (ECL) cells and mast cells. A microdialysis probe was inserted into the gastric submucosa, and the celiac artery was clamped (30 min), followed by removal of the clamp. Microdialysate histamine was determined by enzyme-linked immunosorbent assay. In addition, we studied the long-term effects of ischemia on the oxyntic mucosal histidine decarboxylase activity in omeprazole-treated rats. Gastric mucosal lesions induced by the ischemia were enlarged on removal of the clamp. The microdialysate histamine concentration increased immediately on clamping (50-fold rise within 30 min) and declined promptly after the clamp was removed. In contrast, histidine decarboxylase activity of the ECL cells was lowered by the ischemia and returned to preischemic values 9 days later. Mast cell-deficient rats responded to ischemiareperfusion much like wild-type rats with respect to histamine mobilization. Pretreatment with the irreversible inhibitor of histidine decarboxylase, ␣-fluoromethylhistidine, which is known to eliminate histamine from ECL cells, prevented the rise in microdialysate histamine. Pharmacological blockade of acid secretion (cimetidine or omeprazole) prevented the lesions induced by ischemia-reperfusion insult but not the mobilization of histamine. In conclusion, ischemia of the celiac artery mobilizes large amounts of histamine from ECL cells, which occurs independently of the gross mucosal lesions. The prompt reduction of the mucosal histidine decarboxylase activity in response to ischemia probably reflects ECL cell damage. The lesions develop not because of mobilization of histamine per se but because of ischemia plus reperfusion plus gastric acid. enterochromaffin-like cell; ischemia-reperfusion; histidine decarboxylase THE GASTRIC MUCOSAL INJURY induced by ischemia-reperfusion is a useful experimental model for the study of stress ulcer formation. Clamping the celiac artery for 30 min (ischemia) followed by removal of the clamp (reperfusion) induces gross damage to the oxyntic mucosa, resulting in the formation of petechiae and sometimes ulcers deep down in the mucosa (28).

Microdialysis Monitoring of Biomarkers for Early Recognition of Intestinal Ischemia

“…Microdialysis monitoring of gastric ischemia during temporary celiac artery occlusion in anesthetised rats showed a more remarkable response to ischemia in the relative changes of metabolic ratios of lactate/pyruvate and lactate/glucose compared to changes in the flow indicator of H2O efflux and glycerol (105). Histamine release from enterochromaffin-like (ECL) cells during ischemia has been commonly sampled from the stomach submucosa with a single microdialysis probe (106)(107)(108)(109). However, submucosal microdialysis sampling has been suggested to be unrepresentative of histamine levels released from ECL cells, since these are located in the mucosa layer, requiring a diffusion of histamine from the mucosa to the submucosa and finally to the probe (110).…”

Ischemia mobilizes histamine but not pancreastatin from ECL cells of rat stomach: evidence for a cytosolic histamine compartment

“…Furthermore, microinfusion of the vasoconstrictor endothelin into the submucosa of the rat stomach causes local oxyntic mucosal injury (Whittle 1993;Norlén et al 2001;Bernsand et al 2003) and mobilizes large amounts of ECL-cell histamine (Norlén et al 2001;Bernsand et al 2003). Since both arterial clamping and endothelin microinfusion cause ischemia, we have suggested that hypoxia/anoxia contributes to the erosion of the mucosa and to the mobilization of histamine Kitano et al 2005).…”

“…Clamping of the celiac artery for 30 min leads to extensive oxyntic mucosal damage (Kawai et al 1994) and causes mobilization of large amounts of histamine (Kitano et al 2005). Furthermore, microinfusion of the vasoconstrictor endothelin into the submucosa of the rat stomach causes local oxyntic mucosal injury (Whittle 1993;Norlén et al 2001;Bernsand et al 2003) and mobilizes large amounts of ECL-cell histamine (Norlén et al 2001;Bernsand et al 2003).…”

“…Whereas microinfusion of gastrin causes sustained histamine secretion (at most a fivefold increase), arterial clamping or microinfusion of endothelin induces a large but short-lasting histamine release (an almost 50-fold peak increase; Norlén et al 2001;Bernsand et al 2003;Kitano et al 2005).…”

The development of multiple probe microdialysis sampling in the stomach

“…Microdialysis sampling in the stomach is presently performed with a probe implanted only into the submucosa. Most recently, stomach submucosal microdialysis sampling was used to study histamine release from enterochromaffin-like (ECL) cells [6][7][8][9]. ECL cells are; however, located in the mucosa layer while the microdialysis probes were implanted in the submucosa layer.…”