Increased oxygen consumption caused by cAMP- and Ca (2+) -mediated chloride secretion in rat distal colon
Saraví, F.D.; Cincunegui, L.M.; Saldeña, T.A.; Carra, G.E.; Ibáñez, J.E.
Acta Gastroenterologica Latinoamericana 35(1): 13-18
2005
ISSN/ISBN: 0300-9033 PMID: 15954731 Document Number: 588890
Epithelial ion transport is dependent on ATP supply provided by aerobic metabolism. In the rat distal colon chloride secretion accounts for the largest portion of electrogenic transport measured as the short-circuit current (I-SC). Inhibition of basal chloride secretion decreases epithelial oxygen consumption (QO(2)) in this tissue, while serotonin (5-hydroxytryptamine) proportionally increases both Isc and QO(2). The effect of serotonin in this tissue is mainly mediated by 5HT4 receptors linked to adenylate cyclase through a stimulant G protein (GS). This work assessed whether the chloride secretion-induced increase in QO(2) is a common characteristic Of secretagogues, which act through either cAMP-dependent or Ca2+-dependent mechanisms. The effects of phosphodiesterase inhibitor 3-isobutyl-1-methylxantine (IBMX) and muscarinic agonist carbachol (both 0.1 mmol/L) were studied in rat distal colon isolated mucosa mounted in an Ussing chamber adapted for continuous measurement of oxygen concentration, allowing determination of QO(2). Baseline ISC and QO(2) were compared with ISC and QO(2) after addition of either serotonin as an active control, IBMX, carbachol or IBMX plus carbachol. Each drug increased proportionally Isc and QO(2). Although the effect of IBMX alone was modest and that of carbachol was short-lived, a synergic effect on Isc and QO(2) was seen when both drugs were simultaneously added. Linear regression analysis showed a significant correlation between increases in ISC and QO(2) (r(2) = 0.746; P < 0.0001). Thus, stimulation of chloride secretion increases QO(2) regardless of the intracellular pathway involved. These results extend previous findings, corroborating the close coupling between chloride secretion and QO(2) in this epithelium.