Mode of action of ANG II on ion transport in guinea pig distal colon

Abstract

The effect of ANG II on mucosal ion transport and localization of ANG type 1 receptor (AT1R) in the guinea pig distal colon was investigated. Submucosal/mucosal segments were mounted in Ussing flux chambers, and short-circuit current ( I sc) was measured as an index of ion transport. Serosal addition of ANG II produced a concentration-dependent (10− 9–10− 5M) increase in I sc. The maximal response was observed at 10− 6 M; the increase in I sc was 164.4 ± 11.8 μA/cm2. The ANG II (10− 6 M)-evoked response was mainly due to Cl− secretion. Tetrodotoxin, atropine, the neurokinin type 1 receptor antagonist FK-888, and piroxicam significantly reduced the ANG II (10− 6M)-evoked response to 28, 45, 58, and 16% of control, respectively. Pretreatment with prostaglandin E2(10− 5 M) resulted in a threefold increase in the ANG II-evoked response. The AT1R antagonist FR-130739 completely blocked ANG II (10− 6M)-evoked responses, whereas the ANG type 2 receptor antagonist PD-123319 had no effect. Localization of AT1R was determined by immunohistochemistry. In the immunohistochemical study, AT1R-immunopositive cells were distributed clearly in enteric nerves and moderately in surface epithelial cells. These results suggest that ANG II-evoked electrogenic Cl−secretion may involve submucosal cholinergic and tachykinergic neurons and prostanoid synthesis pathways through AT1R on the submucosal plexus and surface epithelial cells in guinea pig distal colon.