Mechanism of intestinal absorption. Effect of clonidine on rabbit ileal villus and crypt cells.
In intact tissue studies, intestinal absorptogogues stimulate NaCl absorption that occurs via the dual operation of Na:H and Cl:HCO3 exchanges on the brush border membrane (BBM) of villus cells. To determine the cellular mechanism of action of an intestinal absorptogogue, the effect of clonidine was determined on Na:H and Cl:HCO3 exchange in rabbit ileal villus and crypt cells. Using 2,7-bis(carboxyethyl)-5,6-carboxy-fluorescein we have previously shown that recovery from an acid load occurs via Na:H exchange, whereas recovery from an alkaline load occurs via Cl:HCO3 exchange in both cells. In villus cells, the rate of recovery from a propionate-induced alkaline load was not altered by clonidine. However, clonidine stimulated recovery from an acid load induced by NH4Cl, Na removal, or amiloride. These data suggest that clonidine stimulates Na:H exchange in villus cells. In crypt cells, the rate of recovery from a propionate-induced alkaline load was also not altered by clonidine. However, in crypt cells, unlike the villus cells, clonidine inhibited recovery from an acid load induced by NH4Cl, Na removal, or amiloride. These data suggest that clonidine inhibits Na:H exchange in crypt cells. Stimulation of Na:H exchange on the BBM of villus cells would be expected to stimulate coupled NaCl absorption (which occurs by coupling of Na:H and Cl:HCO3 exchange). Inhibition of Na:H in crypt cells, known to be present only on the basolateral membrane, will acidify the cell and may inhibit Cl:HCO3 exchange on the BBM, resulting in the inhibition of HCO3 secretion.
Sundaram
U
U
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D003000:Clonidine / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007082:Ileum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008954:Models, Biological; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors
D017923:Sodium-Hydrogen Exchangers; D012964:Sodium; D003000:Clonidine