Regulatory role of cAMP in transport of Na+, Cl- and short-chain fatty acids across sheep ruminal epithelium

Sodium is absorbed in considerable amounts across the ruminal epithelium, w hilst its transport is strongly interrelated with the permeation of chlorid e and short-chain fatty acids (SCFAs). However, regulation of ruminal Na+, Cl-, and SCFA absorption is hardly understood. The present study was theref ore performed to characterize the influence of cAMP on sodium and sodium-co upled transport mechanisms in short-circuited, stripped ruminal epithelia o f sheep. Elevation of intracellular cAMP concentrations by theophylline (10 mM) or theophylline in combination with forskolin (0.1 mM) significantly r educed mucosal-to-serosal sodium transport, leading to a reduction of net t ransport. The theophylline- or theophylline-forskolin-induced reduction of sodium transport was accompanied by a decrease in chloride net transport bu t revealed no effect on propionate flux. Short-chain fatty acids stimulated Na+ transport but their stimulatory effect was almost completely blocked b y theophylline-forskolin. In solutions with and without SCFAs, the inhibito ry effect of 1 mM amiloride on sodium transport was strongly reduced after theophylline-forskolin pretreatment of the tissues. Blocking the production of endogenous prostaglandins by addition of indomethacin (10 mu M) led to a theophylline-sensitive stimulation of unidirectional and net fluxes of so dium. The findings indicate that apical, amiloride sensitive Na+-H+ exchang e and/or basolateral Na+-K+-ATPase can effectively be blocked by cAMP, lead ing to a decrease in sodium and chloride transport. In the ruminal epitheli um, cAMP is a second messenger of prostaglandins, which are released sponta neously under ill vitro conditions.