The effect of angiotensin II upon electrogenic ion transport in rat intestinal epithelia

Epithelial sheets from rat jejunum and descending colon have been shown to respond to angiotensin II (AII) when studied under short-circuit conditions and bathed on both sides with Krebs-Henseleit solution. The octapeptide AII elicited increases in short-circuit current (SCC) in preparations of jejunum and decreases in SCC in the descending colon; both responses occurred when the peptide was applied to the basolateral surface, but not when applied to the apical solution. Responses in both tissues were highly specific, being inhibited by a range of AII antagonists with the following order of potency: [Sar1. Thr8]-AII greater than [Sar1. Leu8]-AII greater than [Sar1. Ile8]-AII greater than [Sar1. Ala8]-AII greater than [Des,Asp1. Ile8]-AII in rat jejunum. AII responses were not affected by alpha- or beta- adrenoceptor antagonists, atropine or tetrodotoxin. AII responses were totally inhibited by the chloride channel blocker, diphenylamine-2-carboxylate (DPC) while cotransport inhibitors e.g. piretanide and frusemide significantly reduced the size of AII responses in colon and jejunum. These patterns of activity suggest that in the jejunum the responses result from electrogenic chloride secretion. Although AII responses in colon were sensitive to DPC the transporting ions have not yet been identified. Both piroxicam and indomethacin inhibited the increase in SCC elicited by AII in the jejunum, and the reduction in SCC caused by AII in the colon. Taken together these results indicate that eicosanoids are involved in AII responses in both tissues. This is the first study to demonstrate a direct, electrogenic effect for AII on transporting epithelia from the gastrointestinal tract. The responses are most probably initiated by All interacting with previously identified specific All receptors within the epithelial membranes.