Histamine-induced chloride secretion is mediated via H 2 -receptors in the pig proximal colon

Autor: Jörg R. Aschenbach, Frank Ahrens, Gotthold Gäbel, B. Garz
Rok vydání: 2003
Předmět:
Zdroj: Inflammation Research. 52:79-85
ISSN: 1420-908X
1023-3830
DOI: 10.1007/s000110300005
Popis: Objective: The aim of this study was to investigate the action of histamine on function of epithelia in the pig proximal colon.¶Material and methods: Isolated epithelia of the pig proximal colon were prepared by slide-stripping and mounted in Ussing chambers. Short-circuit current (Isc) was measured after serosal addition of histamine (20 μmol/l) with or without pretreatment with histamine receptor antagonists (H1: chlorpyramine, 10 μmol/l; H2: famotidine, 100 μmol/l; H3: thioperamide, 10 μmol/l), a cyclooxygenase inhibitor (indomethacin, 10 μmol/l), or a neuronal conduction blocker (tetrodotoxin, 1 μmol/l). Alternatively, histamine receptor agonists (H1: 2-pyridylethylamine; H2: dimaprit; H3: R-α-methylhistamine, each 100 μmol/l) were added to the serosal side. Flux studies using 14C-mannitol, 22Na+ and 36Cl– were performed in the presence of 100 μmol/l histamine on the serosal side.¶Results: Serosal application of histamine induced a rapid rise in Isc with a maximum 3 min after addition, followed by a slow decrease. Only pretreatment with famotidine decreased the epithelial response to histamine. Pretreatments with chlorpyramine, thioperamide, indomethacin or tetrodotoxin did not change histamine-induced increases in Isc. Action of histamine could be simulated by dimaprit, but not by 2-pyridylethylamine or R-α-methylhistamine. Histamine induced an increase in serosal-to-mucosal chloride flux leading to a decrease of chloride net absorption. Fluxes of sodium and mannitol were not affected by histamine.¶Conclusions: In contrast to the importance of H1-receptors in other gut epithelia, histamine acts directly via H2-receptors in the porcine proximal colon. Changes in Isc after histamine addition are primarily due to chloride secretion. The paracellular permeability is not influenced by histamine.
Databáze: OpenAIRE
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