Effect of Escherichia coli heat‐stable enterotoxin, cholera toxin and theophylline on ion transport in porcine colon

Abstract

SUMMARY1. The effect of heat-stable enterotoxin (ST) of Escherichia coli, cholera toxin (CT), and theophylline (a phosphodiesterase inhibitor) on ion and water transport was studied with an in vivo isolated loop system of the pig colon.2. All three agents abolished net Na absorption as a result ofa decrease in the lumen to blood Na flux alone. With all three agents, net Cl absorption was reduced, but not abolished, and net HCO3 secretion was elicited. Luminal Pco, was reduced with CT and theophylline from that observed in normal Ringer alone.3. Theophylline resulted in a prompt and sustained increase in both cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP) levels in colonic mucosa studied in vitro. ST selectively elevated cyclic GMP, whereas CT selectively elevated cyclic AMP. These responses paralleled the time course and magnitude of response of the transepithelial electrical potential difference (V*LB) measured in vivo.4. Ion replacement studies in the presence or absence of theophylline showed that in the absence of Na, Cl absorption was slightly reduced and HCO3 secretion was elicited; no further additive effects of theophylline in the absence of luminal Na were observed. In the absence of luminal Cl, net Na absorption was abolished and HCO3 was absorbed; theophylline resulted in significant net Na and HCO3 secretion.

Effects of calcitriol on stimulation of ion transport in pig jejunal mucosa.

“…Prior studies have demonstrated that theophylline increases cyclic AMP and cyclic GMP concentrations in pig jejunum (Argenzio & Whipp, 1981; of abolished the theophylline-induced increase in IS, (Fig. 3).…”

“…Cholera toxin, the Ca2+ ionophore A23187 and theophylline, for example, stimulate Na+ and Cl-transport in pig intestinal mucosa by elevating both intracellular Ca2+ and cyclic nucleotide concentrations (Argenzio & Whipp, 1981; Argenzio, Liacos, Berschneider, Whipp & Robertson, 1984;Forsyth, Wong & Maenz, 1985;Maenz, Gabriel & Forsyth, 1987). Participation of Ca2+ in exerting ionic secretion by cholera toxin in isolated porcine enterocytes was suggested from the observation that [Ca2+]i was elevated (Maenz et al 1987), and from the increased influx of Ca2+ into jejunal brush-border membrane vesicles after addition of the toxin (Maenz & Forsyth, 1986).…”

Environmental Influences in the Etiology of Colorectal Cancer: the Premise of Metabolomics

“…These acids could effectively lower the pH of the colon if produced in excess, however bicarbonate secretion, controlled by cellular carbonic anhydrase, ensures that colonic pH is maintained at approximately pH 7.4 (89). This balance can be effected by multiple processes, including bacteria exotoxins which can stimulate bicarbonate secretion (90), or by disease, cancer cells produce elevated levels of lactic acid and protons which modify carbonic anhydrases enabling the cancer cells to survive (19, 91). In addition to host cellular processes, environmental changes caused by switches in diet, microbial infection, or drug treatment, can cause a modulation of the microbial communities within the colon.…”

Mechanisms of Colonic Electrolyte Absorption and Secretion

“…The heat-stable enterotoxin of Escheri chia coli increases the short-circuit current (probably reflecting a rise in electrogenic Cl secretion) and mucosal cyclic GMP levels when added to rabbit caecum [68] and de creases net Na and Cl absorption in pig colon [69]. Clostridium difficile also pro duces an enterotoxin (toxin A) and a cytotoxin (toxin B) which may be partly respon sible for colonic damage in clindamycinrelated pseudomembranous colitis [70], but it is not known whether these toxins stimu late colonic secretion directly.…”