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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/G1019    most recent ajpgi.00255.2009v2 ajpgi.00255.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Casselbrant, A. Articles by Fändriks, L. PubMed PubMed Citation Articles by Casselbrant, A. Articles by Fändriks, L.

HORMONES AND SIGNALING

Angiotensin II receptors are expressed and functional in human esophageal mucosa

Department of Gastrosurgical Research and Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Submitted June 29, 2009 ; accepted in final form September 14, 2009

Only few studies have been devoted to the actions of the renin-angiotensin system (RAS) in the human gastrointestinal tract. The present study was undertaken to elucidate the expression and action of RAS in the human esophageal mucosa. Mucosal specimens with normal histological appearance were obtained from healthy subjects undergoing endoscopy and from patients undergoing esophagectomy due to neoplasm. Gene and protein expressions of angiotensin II (Ang II) receptor type 1 (AT₁) and type 2 (AT₂) and angiotensin-converting enzyme (ACE) were analyzed. In vivo functionality in healthy volunteers was reflected by assessing transmucosal potential difference (PD). Ussing chamber technique was used to analyze the different effects of Ang II on its AT₁ and AT₂ receptors. Immunoreactivity to AT₁ and AT₂ was localized to stratum superficiale and spinosum in the epithelium. ACE, AT₁, and AT₂ were found in blood vessel walls. Transmucosal PD in vivo increased following administration of the AT₁ receptor antagonist candesartan. In Ussing preparations mean basal transmural PD was –6.4 mV, epithelial current (I_ep) 34 µA/cm², and epithelial resistance (R_ep) 321 ·cm². Serosal exposure to Ang II increased PD as a result of increased I_ep, whereas R_ep was constant. Ang II given together with the selective AT₁-receptor antagonist losartan, or AT₂ agonist C21 given alone, resulted in a similar effect. Ang II given in presence of the AT₂-receptor antagonist PD123319 did not influence PD, but I_ep decreased and R_ep increased. In conclusion, Ang II receptors and ACE are expressed in the human esophageal epithelium. The results suggest that AT₂-receptor stimulation increases epithelial ion transport, whereas the AT₁ receptor inhibits ion transport and increases R_ep.

potential difference; epithelial current; epithelial resistance