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Am J Physiol Gastrointest Liver Physiol 278: G625-G634, 2000;
0193-1857/00 $5.00
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Vol. 278, Issue 4, G625-G634, April 2000

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

Yutaka Hosoda1, Adi Winarto2, Toshihiko Iwanaga2, and Atsukazu Kuwahara1

1 Laboratory of Environmental Physiology, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka 422-8526; and 2 Laboratory of Veterinary Anatomy, Hokkaido University, Sapporo 060-0818, Japan

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 (Isc) was measured as an index of ion transport. Serosal addition of ANG II produced a concentration-dependent (10-9-10-5 M) increase in Isc. The maximal response was observed at 10-6 M; the increase in Isc 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 (10-6 M)-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 (10-6 M)-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.

substance P; prostaglandin; local renin-angiotensin system; angiotensin type 1 receptor; neurokinin type 1 receptor


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