Imidazolines inhibit secretory responses of rat colonic mucosa to calcium-dependent but not cyclic AMP-dependent secretagogues.
The purpose of this study was to investigate whether imidazolines have an anti-secretory action on intestinal epithelial cells. Muscle-stripped preparations of rat colon and monolayers of T84 human colonic epithelial cells were set up in Ussing chambers for measurement of short-circuit current. In rat colon acetylcholine, histamine, vasoactive intestinal polypeptide and forskolin elicited secretory responses which were recorded as increases in short-circuit current. Secretory responses to acetylcholine were inhibited in a concentration-dependent manner by the imidazolines phentolamine, idazoxan and clonidine. The effect of clonidine was not reversed by pre-incubation of mucosal preparations with yohimbine. Secretory responses to vasoactive intestinal polypeptide were unaffected by the three imidazolines. Phentolamine reduced responses of colonic mucosa to histamine but had no effect on responses to forskolin. Responses to vasoactive intestinal polypeptide and forskolin were significantly reduced in the presence of barium. In T84 cell monolayers phentolamine significantly reduced responses to acetylcholine. Three imidazolines, two with alpha-adrenoceptor-antagonist properties and one with alpha-agonist properties, have anti-secretory effects in rat colonic mucosal preparations. The anti-secretory action appears to discriminate between calcium-dependent and cyclic AMP-dependent secretagogues, inhibiting the former but not the latter.
Division of Biomedical Sciences, Queen Mary and Westfield College, University of London, UK.
M
M
Anderson
D
D
Burleigh
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology*; D019329:Idazoxan / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D000242:Cyclic AMP; D003000:Clonidine; D002118:Calcium; D019329:Idazoxan; D010646:Phentolamine