Histamine-induced chloride secretion is mediated via H2-receptors in the pig proximal colon.
OBJECTIVE
The aim of this study was to investigate the action of histamine on function of epithelia in the pig proximal colon.


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 micromol/l) with or without pretreatment with histamine receptor antagonists (H1: chlorpyramine, 10 micromol/l; H2: famotidine, 100 micromol/l; H3: thioperamide, 10 micromol/l), a cyclooxygenase inhibitor (indomethacin, 10 micromol/l), or a neuronal conduction blocker (tetrodotoxin, 1 micromol/l). Alternatively, histamine receptor agonists (H1: 2-pyridylethylamine; H2: dimaprit; H3: R-alpha-methylhistamine, each 100 micromol/l) were added to the serosal side. Flux studies using 14C-mannitol, 22Na+ and 36Cl- were performed in the presence of 100 micromol/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-alpha-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.
Ahrens
F
F
Institute for Animal Welfare, Ethology and Animal Hygiene, Ludwig-Maximilians-University, Munich, Schwere-Reiter-Strasse 9, D-80797 Munich, Germany. f.ahrens@tierhyg.vetmed.uni-muenchen.de
Gäbel
G
G
Garz
B
B
Aschenbach
J R
JR
D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000378:metabolism* / Q000502:physiology; D004553:Electric Conductivity; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D011970:Receptors, Histamine H2 / Q000502:physiology*; D013552:Swine
D002712:Chlorides; D011970:Receptors, Histamine H2; D006632:Histamine