Uptake and methylation of histamine by dispersed gastric mucosal cells and its possible influence on acid secretion.
Inactivation of histamine by gastric mucosal tissue was examined in dispersed rabbit gastric mucosal cells. Mucosal cells were incubated with [14C]histamine. The formed radioactive metabolites were separated and identified by thin layer co-chromatography and quantitated, in both the cellular and extracellular mediums. Gastric mucosal cells internalized histamine, most of which was immediately methylated primarily to N tau-methylhistamine and released. Cellular histamine product accumulation reached a plateau. The rate of histamine methylation increased with increasing extracellular histamine concentration, moving towards a plateau above 5 microM. Histamine methylation was greatly decreased but not abolished at 4 degrees C, in the absence of Na+ and by phlorizin (0.5 mM), an inhibitor of Na(+)-dependent co-transport. Inhibition of histamine N-methyltransferase decreased intracellular methylhistamine content dose dependently without increasing intracellular histamine. The secretagogues pentagastrin and carbachol did not influence histamine metabolism but ethanol inhibited methylation. The data suggest that gastric mucosal cells take up histamine by a Na(+)-dependent and Na(+)-independent process. The histamine uptake capacity appears to be linked to the methylation activity within the cell. The decrease in histamine uptake and metabolism caused by ethanol could potentially increase histamine concentrations near the target cells and be the reason for the stimulatory effect of ethanol on acid secretion.
Wollin
A
A
Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D000431:Ethanol / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism*; D006637:Histamine N-Methyltransferase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D008745:Methylation; D008854:Microscopy, Electron; D010418:Pentagastrin / Q000494:pharmacology; D011817:Rabbits
D007202:Indicators and Reagents; D000431:Ethanol; D006632:Histamine; D002217:Carbachol; D006637:Histamine N-Methyltransferase; D010418:Pentagastrin