NH(4)Cl inhibition of acid secretion: possible involvement of an apical K(+) channel in bullfrog oxyntic cells.
This study was undertaken to determine the mechanism by which ammonium chloride (NH(4)Cl) inhibits stimulated acid secretion in the bullfrog gastric mucosa. To this end, four possible pathways of inhibition were studied: 1) blockade of basolateral K(+) channel, 2) blockade of ion transport activity, 3) neutralization of secreted H(+) in the luminal solution, or 4) ATP depletion. Addition of nutrient 10 mM NH(4)Cl (calculated NH(3) concentration = 92.5 microM and NH(4)(+) concentration = 9.91 mM) inhibited acid secretion within 30 min. Inhibition of acid secretion did not occur by blockade of basolateral K(+) channel activity or ion transport activity or by neutralization of the luminal solution. Although ATP depletion occurred in the presence of NH(4)Cl, the magnitude of ATP depletion in 30 min was not sufficient to inhibit stimulated acid secretion. By comparing the effect of NH(4)Cl on the resistance of inhibited or stimulated tissues, we demonstrate that NH(4)Cl acts specifically on stimulated tissues. We propose that NH(4)Cl blocks activity of an apical K(+) channel present in stimulated oxyntic cells. Our data suggest that the activity of this channel is important for the regulation of acid secretion in bullfrog oxyntic cells.
Hagen
S J
SJ
Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. shagen@caregroup.harvard.edu
Wu
H
H
Morrison
S W
SW
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002034:Bumetanide / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002250:Carbon Radioisotopes; D018678:Cholinergic Agents / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003022:Clotrimazole / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006851:Hydrochloric Acid / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008744:Methylamines / Q000494:pharmacology; D008854:Microscopy, Electron; D009853:Omeprazole / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011522:Protons; D011892:Rana catesbeiana; D019789:Tetraethylammonium / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
D002250:Carbon Radioisotopes; D018678:Cholinergic Agents; D004232:Diuretics; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D007004:Hypoglycemic Agents; D007093:Imidazoles; D008744:Methylamines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011522:Protons; D000643:Ammonium Chloride; D002034:Bumetanide; D001464:Barium; D010042:Ouabain; D019789:Tetraethylammonium; D000641:Ammonia; C029899:imidazole; D002927:Cimetidine; D006632:Histamine; D000255:Adenosine Triphosphate; D002217:Carbachol; D014044:Tolbutamide; C027451:methylamine; D003022:Clotrimazole; D009853:Omeprazole; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D006851:Hydrochloric Acid