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

Cox, Helen; Cuthbert, A. W.; Munday, K. A.

doi:10.1111/j.1476-5381.1987.tb08969.x

Cited by 42 publications

(32 citation statements)

References 19 publications

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“…High-affinity binding sites for Ang II have been identified on intestinal epithelium (Cox et al 1986) but their location referred rather to the basolateral membrane of enterocytes (Cox et al 1987). Therefore, the most likely target tissue remains the pancreas itself as AT1 and AT2 receptors have been detected on the luminal pole of the duct and acinar cells .…”

Section: Discussionmentioning

confidence: 99%

Angiotensinogen localization and secretion in the rat pancreas

Regoli

Bendayan²,

Fonzi³

et al. 2003

Journal of Endocrinology

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Renin and angiotensinogen have been previously found in the rat pancreas, and angiotensin receptors have been located in the apical domain of duct cells. To evaluate the possibility that angiotensin II could be generated within the duct system, we decided to determine whether angiotensinogen is present in rat pancreatic juice and the angiotensinogen-immunoreactive pancreatic cell types that could be responsible for its production. Angiotensinogen was detected in significant amounts by Western blotting in pancreatic juice collected from several individual rats. Different isoforms between plasma and pancreatic juice angiotensinogens were demonstrated by isoelectric focusing. Immunocytochemical experiments revealed angiotensinogen-immunoreactive cells at the periphery of the islets of Langerhans, and confocal microscopy demonstrated that most angiotensinogenimmunoreactive cells were glucagon-secreting cells. Secretion of angiotensinogen did not follow the regulated secretory pathway since it was absent from the glucagoncontaining granules. This was confirmed by electron microscopy immunocytochemistry. Duct and acinar cells did not express angiotensinogen at an immunocytochemical detectable level. The present findings indicated an exocrine secretion of angiotensinogen by glucagonsecreting cells and suggest that one of the final targets of the local pancreatic renin-angiotensin system may be the duct epithelium.

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Section: Discussionmentioning

confidence: 99%

Angiotensinogen localization and secretion in the rat pancreas

Regoli

Bendayan²,

Fonzi³

et al. 2003

Journal of Endocrinology

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“…Both could be blocked by PD or L-NAME, suggesting that the effects of sodium restriction occur via ANG II at the AT 2 receptor. L-ARG-stimulated fluid absorption was blocked by the soluble guanylyl cyclase inhibitor 1-H- [1,2,4]oxadiazolo[4,2-α]quinoxalin-1-one (ODQ). Cyclic GMP-specific phosphodiesterase in the interstitial space decreased extracellular cGMP content and prevented the absorptive effects of L-ARG.…”

Section: Methodsmentioning

confidence: 99%

“…Angiotensin II (ANG II) regulates sodium and water transport across epithelial cells in the kidney and gastrointestinal tract (1)(2)(3)(4)(5). In the jejunum, low concentrations of ANG II stimulate sodium and water absorption while high concentrations inhibit absorption and/or stimulate secretion (3).…”

Section: Introductionmentioning

confidence: 99%

Compartmentalization of extracellular cGMP determines absorptive or secretory responses in the rat jejunum

Jin

Siragy²,

Guerrant³

et al. 1999

J. Clin. Invest.

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Angiotensin II (ANG II) regulates sodium and water transport across epithelial cells in the kidney and gastrointestinal tract (1-5). In the jejunum, low concentrations of ANG II stimulate sodium and water absorption while high concentrations inhibit absorption and/or stimulate secretion (3). We have recently demonstrated that ANG II stimulates absorption in the jejunum by an action at the AT 2 receptor involving the generation of guanosine cyclic 3′,5′-monophosphate (cGMP) (3,6,7).In this study, we hypothesized that ANG II increases jejunal sodium and water absorption by increasing the synthesis of nitric oxide (NO) and stimulating soluble guanylyl cyclase. However, since cGMP is thought to mediate secretory, not absorptive, responses in the gastrointestinal tract when particulate guanylyl cyclase (GC-C) is stimulated by the heat-stable enterotoxin of Escherichia coli (STa) or guanylin or uroguanylin (8, 9), we hypothesized that the sodium and water transport response, absorptive or secretory, is associated with a compartmentalized cGMP response via either soluble or particulate guanylyl cyclase. If so, STa would stimulate secretion by stimulating particulate guanylyl cyclase on the apical cell membrane of transporting epithelial cells. In contradistinction, nitric oxide would stimulate absorption via soluble guanylyl cyclase from the serosal side, and cGMP would be released predominantly across the basolateral membrane of epithelial cells into the interstitial space. We introduced both in situ loop and microdialysis techniques to test these hypotheses. MethodsAnimal preparation. Male Wistar rats weighing 200 ± 15 g were obtained from Harlan Bioproducts Inc. (Indianapolis, Indiana, USA). Rats were housed in a room with 12-h light-dark cycles and maintained on standard rat chow containing 0.28% NaCl or low-sodium chow containing 0.08% NaCl (BioServe Biotechnologies, Frenchtown, New Jersey, USA). Rats were fasted overnight before the study.Operative procedure. Rats (n = 8 in each group) were anesthetized with pentobarbital sodium 70 mg/kg intraperitoneally (Veterinary Laboratories, Inc., Lenexa, Kansas). The trachea and left jugular vein were cannulated. A venous cannula (PE 50) was connected to a Harvard 975 infusion pump (Harvard Apparatus Co., South Natick, Massachusetts, USA) through which lactated Ringer's solution (vehicle) and drugs were infused. A ventral midline celiotomy also was performed and the jejunum was prepared in two different ways as described below.Single-pass perfusion. These studies were performed according to previous publications (10, 11). An inlet cannula was placed just below the duodenal-jejunal flexure and the outlet cannula was 15 cm distal to the inlet cannula. The lumen just proximal and distal to the cannulated segment was tied off. To measure water transport, lactated Ringer's solution containing [ 14 C]inulin (15,000 dpm/ml; 2.2 µCi/mg specific activity; New England Nuclear, Boston, Massachusetts, USA) and phenol red (50 mg/liter, Sigma Chemical Company; St. Louis, Missouri, We ex...

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“…pharmacological and morphological studies has established roles for angiotensin II (Ang II) on GI epithelial transport processes [1][2][3] and motor activity. [4][5][6] Today, the RAS is regarded not only as an endocrine system, but can also be locally expressed and involve several bioactive angiotensinogen fragments.…”

Section: Introductionmentioning

confidence: 99%

The angiotensin II type 2 receptor and the gastrointestinal tract

Fändriks

2009

J Renin Angiotensin Aldosterone Syst

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The renin-angiotensin system (RAS) is well known for its vital involvement in body fluid homeostasis and circulation. However, very little research has been devoted to the impact of this regulatory system on the gastrointestinal (GI) system. This is surprising because the GI tract is fundamental for the intake and excretion of fluid and electrolytes (and nutrients), and it accommodates a large proportion of bodily haemodynamics and host defence systems. The RAS is well expressed and active in the GI tract, although the exact roles for the key mediator angiotensin II (Ang II) and its receptors in general, and the type 2 (AT 2 ) receptor in particular, are not completely settled. There are several reports showing Ang II regulation of intestinal fluid and electrolyte transport. For example, mucosaprotective duodenal bicarbonate-rich secretion is inhibited by Ang II via type 1 (AT 1 ) receptor-mediated facilitation of sympathoadrenergic activity, but this secretory process can also be stimulated by Ang II via AT 2 receptors. Novel data from human oesophagus and jejunum suggest that the AT 1 receptor mediates muscular contractions and that the AT 2 receptor regulates epithelial functions. Data are accumulating suggesting involvement of AT 1 and AT 2 receptors in GI inflammation and carcinogenesis. The picture of the RAS and AT 2 receptor in the GI tract is, however, far from complete. Much more basic research is needed with regard to GI pathophysiology before concluding clinical significance and potential applicability of pharmacological interferences with the RAS.

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

Cited by 42 publications

References 19 publications

Angiotensinogen localization and secretion in the rat pancreas

Angiotensinogen localization and secretion in the rat pancreas

Compartmentalization of extracellular cGMP determines absorptive or secretory responses in the rat jejunum

The angiotensin II type 2 receptor and the gastrointestinal tract

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