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 (AT(1)R) 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(-5) M) increase in I(sc). The maximal response was observed at 10(-6) M; the increase in I(sc) was 164.4 +/- 11.8 microA/cm(2). 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 E(2) (10(-5) M) resulted in a threefold increase in the ANG II-evoked response. The AT(1)R 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 AT(1)R was determined by immunohistochemistry. In the immunohistochemical study, AT(1)R-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 AT(1)R on the submucosal plexus and surface epithelial cells in guinea pig distal colon.

Cyclooxygenase-2 Inhibitors Attenuate Angiotensin II–Induced Oxidative Stress, Hypertension, and Cardiac Hypertrophy in Rats

“…Our present results showed that Ang II-stimulated O 2 Ϫ ⅐ generation was observed only in cardiovascular tissues but not in colon, although previous studies have demonstrated the presence and the functions of AT1 and AT2 receptors in colon. 19 Our results have also shown that Ang II selectively stimulated cardiac COX-2 but not COX-1 enzyme expression in vivo. Similar result was also reported by Young et al 10 on cultured SMCs.…”

Stimulation of chloride secretion by baicalein in isolated rat distal colon

“…This is in contrast with angiotensin II-and substance P-evoked Cl Ϫ secretory response, which involves submucosal cholinergic neurons (13,21). Therefore, baicalein may act directly on epithelial or subepithelial cells in the mucosa to evoke Cl Ϫ secretion, which involves PG synthesis.…”

Cellular Signaling Mechanisms Underlying Pharmacological Action of Bak Foong Pills on Gastrointestinal Secretion.

“…Secretagogue-induced Cl Ϫ secretion by the GI tract is important because Cl Ϫ secretion provides an essential driving force for the lubrication of intestinal contents during regular bowl movements or the flushing of microbial organisms or artificial irritants in host defense responses [2,3]. Epithelial Cl Ϫ channels, especially the cAMP-activated Cl Ϫ channels, play an important role in regulating and maintaining the normal physiological functions of the GI tract.…”

“…Z980035) that has long been used for treating gynecological disorders and improving of overall body functions, including gastrointestinal (GI) function [1]. However, the cellular signaling mechanism underlying BFP action, especially on the GI tract, has not been elucidated.Secretagogue-induced Cl Ϫ secretion by the GI tract is important because Cl Ϫ secretion provides an essential driving force for the lubrication of intestinal contents during regular bowl movements or the flushing of microbial organisms or artificial irritants in host defense responses [2,3]. Epithelial Cl Ϫ channels, especially the cAMP-activated Cl Ϫ channels, play an important role in regulating and maintaining the normal physiological functions of the GI tract.…”