Role of gap junctions in inhibiting ischemia-reperfusion injury of rat gastric mucosa.
Gap junctional intercellular communication (GJIC) is known to be important in the maintenance of tissue homeostasis. However, the role of GJIC in gastric mucosa has not been well investigated. We tested the hypothesis that maintenance of GJIC protects rat gastric mucosa against ischemia-reperfusion (I/R) stress by using irsogladine, an activator of GJIC, and octanol, an inhibitor of GJIC. Intragastric perfusion with octanol before ischemia resulted in a significant increase in 51Cr-EDTA clearance after reperfusion. Intraduodenal pretreatment with irsogladine attenuated the increase in 51Cr-EDTA clearance produced by octanol in a dose-dependent manner. Epithelial gap junctions reacted with anticonnexin-32 monoclonal antibodies were not changed after I/R stress alone. Intragastric perfusion with octanol caused a significant reduction in immunoreactive connexin-32 spots, which was completely reversed by irsogladine. These results indicate that inhibition of GJIC weakens the barrier function of gastric mucosa and subsequently causes damage of the barrier function in combination with I/R. Facilitation of GJIC and maintenance of gap junctions protect gastric mucosal barrier functions by potentiating cellular integrity.
Iwata
F
F
Department of Internal Medicine, NTT Tokai General Hospital, Nagoya 460-0017, Japan.
Joh
T
T
Ueda
F
F
Yokoyama
Y
Y
Itoh
M
M
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal; D002450:Cell Communication; D002860:Chromium Radioisotopes / Q000493:pharmacokinetics; D017630:Connexins / Q000276:immunology / Q000502:physiology; D004492:Edetic Acid / Q000493:pharmacokinetics; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D005753:Gastric Mucosa / Q000098:blood supply* / Q000502:physiology / Q000503:physiopathology; D006706:Homeostasis; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D014227:Triazines / Q000494:pharmacology*; D000097002:Gap Junction beta-1 Protein
D000897:Anti-Ulcer Agents; D000911:Antibodies, Monoclonal; D002860:Chromium Radioisotopes; D017630:Connexins; D004492:Edetic Acid; D014227:Triazines; D000097002:Gap Junction beta-1 Protein; C041836:irsogladine