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Acid transport through gastric mucus: A study in vivo in rats and mice
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The gastric mucosa is frequently exposed to endogenously secreted hydrochloric acid of high acidity. Gastric mucosal defense mechanisms are arranged at different levels of the gastric mucosa and must work in unison to maintain its integrity.

In this thesis, several mechanisms underlying gastric mucosal resistance to strong acid were investigated in anesthetized rats and mice. The main findings were as follows:

Only when acid secretion occurred did the pH gradient in the mucus gel withstand back-diffusion of luminal acid (100 mM or 155 mM HCl), and keep the juxtamucosal pH (pHjm) neutral. Thus, when no acid secretion occurred and the luminal pH was 0.8-1, the pH gradient was destroyed.

Bicarbonate ions, produced concomitant with hydrogen ions in the parietal cells during acid secretion and blood-borne to the surface epithelium, were carried transepithelially through a DIDS-sensitive transport.

Prostaglandin-dependent bicarbonate secretion seemed to be less important in maintaining a neutral pHjm.

Removal of the loosely adherent mucus layer did not influence the maintenance of the pHjm. Hence, only the firmly adherent mucus gel layer, approximately 80µm thick, seemed to be important for the pHjm.

Staining of the mucus gel with a pH-sensitive dye revealed that secreted acid penetrated the mucus gel from the crypt openings toward the gastric lumen only in restricted paths (channels). One crypt opening was attached to one channel, and the channel was irreversibly formed during acid secretion.

Gastric mucosal blood flow increased on application of strong luminal acid (155 mM HCl). This acid-induced hyperemia involved the inducible but not the neural isoform of nitric oxide synthase. These results suggest a novel role for iNOS in gastric mucosal protection and indicate that iNOS is constitutively expressed in the gastric mucosa.

It is concluded that a pH gradient in the gastric mucus gel can be maintained during ongoing acid secretion, since the acid penetrates the mucus only in restricted channels and bicarbonate is carried from the blood to the lumen via a DIDS-sensitive transporter.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2003. , p. 64
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1239
Keywords [en]
Physiology, gastric acid, pH-sensitive microelectrode, mucus, mucosal blood flow, nitric oxide, intravital microscopy, laser Doppler flowmetry
Keywords [sv]
Fysiologi
National Category
Physiology
Research subject
Physiology
Identifiers
URN: urn:nbn:se:uu:diva-3368ISBN: 91-554-5577-8 (print)OAI: oai:DiVA.org:uu-3368DiVA, id: diva2:162515
Public defence
2003-05-09, B22, BMC, Uppsala, 13:15
Opponent
Supervisors
Available from: 2003-04-15 Created: 2003-04-15 Last updated: 2018-01-13Bibliographically approved
List of papers
1. Intraluminal acid and gastric mucosal integrity;the importance of blood-borne bicarbonate
Open this publication in new window or tab >>Intraluminal acid and gastric mucosal integrity;the importance of blood-borne bicarbonate
2001 In: Am J Physiol Gastrointest Liver Physiol, Vol. 280, p. G121-G129Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-90225 (URN)
Available from: 2003-04-15 Created: 2003-04-15 Last updated: 2012-12-14
2.
The record could not be found. The reason may be that the record is no longer available or you may have typed in a wrong id in the address field.
3. The importance of mucus layers and bicarbonate transport in preservation of gastric juxtamucosal pH
Open this publication in new window or tab >>The importance of mucus layers and bicarbonate transport in preservation of gastric juxtamucosal pH
2002 (English)In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 282, no 2, p. G211-G219Article in journal (Refereed) Published
Abstract [en]

Mucus thickness is suggested to be related to mucosal protection. We therefore investigated the importance of the removable mucous layer and epithelial bicarbonate transport in preservation of the gastric juxtamucosal pH (pH(jm)) during luminal acid. Anesthetized rats were prepared for intravital microscopy of the gastric mucosa, and pH(jm) was measured with pH-sensitive microelectrodes. The mucus was either left intact (IM) or removed (MR) down to the firmly attached mucous layer, and HCl (pH 1) was applied luminally. Removal of the loosely adherent mucous layer did not influence the pH(jm) during luminal acid (pentagastrin: IM/MR 7.03 +/- 0.09/6.82 +/- 0.19; pentagastrin + indomethacin: IM/MR 6.89 +/- 0.20/6.95 +/- 0.27; ranitidine: IM/MR 2.38 +/- 0.64/2.97 +/- 0.62), unless prostaglandin synthesis and acid secretion were inhibited (ranitidine + indomethacin: IM/MR 2.03 +/- 0.37/1.66 +/- 0.18). Neutral pH(jm) is maintained during endogenous acid secretion and luminal pH 1, unless DIDS was applied luminally, which resulted in a substantially decreased pH(jm) (1.37 +/- 0.21). Neutral pH(jm) is maintained by a DIDS-sensitive bicarbonate transport over the surface epithelium. The loosely adherent mucous layer only contributes to maintaining pH(jm) during luminal pH 1 if acid secretion and prostaglandin synthesis are inhibited.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-90227 (URN)10.1152/ajpgi.00223.2001 (DOI)11804841 (PubMedID)
Available from: 2003-04-15 Created: 2003-04-15 Last updated: 2017-12-14Bibliographically approved
4.
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