Ischemia mobilizes histamine but not pancreastatin from ECL cells of rat stomach: evidence for a cytosolic histamine compartment.
Histamine in the rat stomach resides in enterochromaffin-like (ECL) cells and mast cells. The ECL cells are peptide-hormone-producing endocrine cells known to release histamine and chromogranin-A-derived peptides (such as pancreastatin) in response to gastrin. Ischemia (induced by clamping of the celiac artery or by gastric submucosal microinfusion of the vasoconstrictor endothelin) mobilizes large amounts of ECL-cell histamine in a burst-like manner. This report examines the ECL-cell response to ischemia and compares it with that induced by gastrin in rats. Arterial clamping (30 min) and gastric submucosal microinfusion (3 h) of endothelin, vasopressin, or adrenaline caused ischemia, manifested as a raised lactate/pyruvate ratio and mucosal damage. Whereas microinfusion of gastrin released both histamine and pancreastatin, ischemia mobilized histamine only. The mucosal concentrations of histamine and pancreastatin, the number and immunostaining intensity of the ECL cells, and the ultrastructure of the ECL cells were unchanged following ischemia. The long-term effects of ischemia and reperfusion (60-90 min) on gastric mucosa were examined in rats treated with the proton pump inhibitor omeprazole for 4 days. The activity of the ECL cells was suppressed (reflected in low histamine-forming capacity) but returned to normal within 1 week, illustrating the ability of the ECL cells to recover. We suggest that ischemia mobilizes cytosolic ECL-cell histamine without affecting the storage of histamine (and pancreastatin) in the secretory organelles and without causing lasting ECL-cell impairment.
Bernsand
Maria
M
Unit of Cellular and Molecular Pharmacology, Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
Zhao
Chun-Mei
CM
Håkanson
Rolf
R
Stenström
Björn
B
Chen
Duan
D
Norlén
Per
P
D000818:Animals; D002451:Cell Compartmentation / Q000502:physiology*; D053379:Chromogranin A; D003600:Cytosol / Q000378:metabolism*; D016232:Endothelins / Q000494:pharmacology; D019861:Enterochromaffin-like Cells / Q000187:drug effects / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005755:Gastrins / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects; D007511:Ischemia / Q000139:chemically induced / Q000378:metabolism*; D010187:Pancreatic Hormones / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D022142:Secretory Vesicles / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology
D053379:Chromogranin A; D016232:Endothelins; D005755:Gastrins; D010187:Pancreatic Hormones; C050836:pancreastatin; D014667:Vasopressins; D006632:Histamine; D004837:Epinephrine