Role of histamine receptors in intestinal repair after ischemia-reperfusion in rats.
OBJECTIVE
Previously, we showed that an elevated production of histamine promotes the healing of injured intestinal mucosa after ischemia-reperfusion. The aim of the present study was to determine whether histamine-mediated repair of the intestinal mucosa after ischemia-reperfusion involves the engagement of H1 or H2 receptors.


METHODS
The superior mesenteric artery was occluded for 15 minutes followed by reperfusion, and H1- or H2-receptor antagonists were infused intraduodenally. After ischemia-reperfusion, ornithine decarboxylase activity in the jejunal mucosa and lipid transport to mesenteric lymph were examined.


RESULTS
In jejunal mucosa, ornithine decarboxylase activity markedly increased at 6 hours after reperfusion and remained elevated at 48 hours. The ischemia-reperfusion-induced increase in ornithine decarboxylase activity was attenuated (in a dose-dependent manner) by an H1-receptor antagonist (chlorpheniramine maleate) but not by an H2 antagonist (cimetidine). Intraperitoneal injection of an H3 antagonist (thioperamide) increased histamine output in mesenteric lymph and stimulated intestinal ornithine decarboxylase activity. Transport of dietary lipid into mesenteric lymph was depressed 24 hours after an ischemic insult, yet it returned to the normal level 48 hours after ischemia-reperfusion. The recovery of the lipid transport normally observed at 48 hours after ischemia-reperfusion was attenuated by the H1 antagonist.


CONCLUSIONS
The beneficial effects of histamine on the repair of intestinal mucosa after ischemia-reperfusion results from the engagement and activation of the H1 receptor.
Tsunada
S
S
Department of Internal Medicine, Saga Medical School, Nabeshima, Japan.
Fujimoto
K
K
Gotoh
Y
Y
Sakai
T
T
Kang
M
M
Sakata
T
T
Granger
D N
DN
Tso
P
P
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004041:Dietary Fats / Q000493:pharmacokinetics; D006633:Histamine Antagonists; D006636:Histamine Release / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D008196:Lymph / Q000378:metabolism; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011968:Receptors, Histamine / Q000502:physiology*; D011969:Receptors, Histamine H1 / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000502:physiology; D015427:Reperfusion Injury / Q000201:enzymology / Q000378:metabolism*
D004041:Dietary Fats; D006633:Histamine Antagonists; D010880:Piperidines; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D002744:Chlorpheniramine; D002927:Cimetidine; D009955:Ornithine Decarboxylase; C052075:thioperamide