Carbachol potentiates cholera toxin-induced secretion in a colonic epithelial cell line (HT29-19A) and rat ileal mucosa in vitro.
Recent studies show that enteric nerves are involved in the action of cholera toxin, both in vivo and in vitro. The aim of this study was to investigate in vitro the influence of carbachol, a cholinergic agonist, on the action of cholera toxin. Cultured HT29-19A cell lines and rat ileal mucosa were used in an Ussing chamber for the measurement of short-circuit current induced by cholera toxin. Cyclic AMP was measured from HT29-19A cell lines by standard radio-immunoassay. Pre-treatment of the HT29-19A cell lines with carbachol potentiated cholera toxin-induced secretory response, and enhanced accumulation of cAMP. Carbachol also potentiated the cholera toxin-secretory response in the rat ileal mucosa, but only following pretreatment with the prostaglandin synthesis inhibitor, indomethacin. There was synergistic interaction between cholera toxin and cholinergic neurotransmitter carbachol on the intestinal epithelium. Cholinergic agonists may play a role in regulating the secretory response to the toxin. Such interaction is masked in the intact tissues in vitro due to the release of prostaglandins during isolation.
Mahmood
B
B
Department of Medicine, Hope Hospital, University of Manchester, School of Medicine, Salford, UK.
Warhurst
G
G
Higgs
N
N
Turnberg
L A
LA
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002772:Cholera Toxin / Q000633:toxicity*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D019073:HT29 Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D018679:Cholinergic Agonists; D016861:Cyclooxygenase Inhibitors; D002217:Carbachol; D002772:Cholera Toxin; D000242:Cyclic AMP; D007213:Indomethacin