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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/G165    most recent 00264.2007v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Larsson, M. H. Articles by Sjövall, H. PubMed PubMed Citation Articles by Larsson, M. H. Articles by Sjövall, H.

MUCOSAL BIOLOGY

Pharmacological analysis of components of the change in transmural potential difference evoked by distension of rat proximal small intestine in vivo

Departments of ¹Integrative Pharmacology, Gastrointestinal Biology and ⁵Clinical Information Science, Biostatistics, AstraZeneca Research and Development, Mölndal, Sweden; ²Department of Neuroscience and Physiology, Section of Physiology, Sahlgrenska Academy, University of Göteborg and ³Department of Internal Medicine, Section of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Göteborg, Sweden; ⁴Department of Physiology, University of Melbourne, Parkville, Victoria, Australia

Submitted 12 June 2007 ; accepted in final form 1 November 2007

The reflex response to distension of the small intestine in vivo is complex and not well understood. The aim of this study was to characterize the neural mechanisms contributing to the complex time course of the intestinal secretory response to distension. Transmucosal potential difference (PD) was used as a marker for mucosal chloride secretion, which reflects the activity of the secretomotor neurons. Graded distensions (5, 10, and 20 mmHg) of distal rat duodenum with saline for 5 min induced a biphasic PD response with an initial peak (rapid response) followed by a plateau (sustained response). The rapid response was significantly reduced by the neural blockers tetrodotoxin and lidocaine (given serosally) and by intravenous (iv) administration of the ganglionic blocker hexamethonium and the NK₁ receptor antagonist SR-140333. Serosal TTX and iv SR-140333 significantly reduced the sustained response, which was also reduced by the NK₃ receptor antagonist talnetant and by the vasoactive intestinal polypeptide (VPAC) receptor antagonist [4Cl-D-Phe⁶, Leu¹⁷]-VIP. Serosal lidocaine and iv hexamethonium had no significant effect on this component. Inhibition of nitric oxide synthase had no effect on any of the components of the PD response to distension. The PD response to distension thus seems to consist of two components, a rapidly activating and adapting component operating via nicotinic transmission and NK₁ receptors, and a slow component operating via VIP-ergic transmission and involving both NK₁ and NK₃ receptors.

mouse; intestinal mucosa; chloride secretion; tachykinin receptors; VIP; nitric oxide; VPAC receptors