Rabbit gut permeability in response to histamine chloramines and chemotactic peptide.
Granulocyte-derived chlorinated amines and bacterial formyl peptides are thought to enhance epithelial permeability. In the current study, gut permeability to [51Cr]ethylenediaminetetraacetic acid (EDTA) was monitored in response to luminal formyl-methionyl-leucyl-phenylalanine (fMLP) and histamine monochloramine and dichloramine. Responses were determined in rabbits during states of basal and elevated permeability. Luminal fMLP had minimal effects of gut permeability in control and injured states. Histamine monochloramine or dichloramine enhanced epithelial permeability under basal conditions; this effect was exaggerated by a pre-existing injury. Both histamine monochloramine and dichloramine retained full histamine agonist properties, and a combination of antioxidant and antihistamine therapy was required to block this increase in gut permeability. Whereas histamine chloramines caused a dose-dependent cytotoxicity in rat-cultured enterocytes, marked histological changes to the mucosa were not evident, nor were mucosal glutathione levels depleted. As histamine chloramines retain the histaminergic and oxidizing potential of their precursors, they represent a unique form of inflammatory mediator, although their highly reactive nature precludes in vivo confirmation of their formation.
Miller
M J
MJ
Department of Pediatrics, Louisiana State University Medical Center, New Orleans.
Zhang
X J
XJ
Barkemeyer
B
B
Grisham
M B
MB
Sadowska-Krowicka
H
H
Eloby-Childress
S
S
Clark
D A
DA
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002630:Chemotactic Factors / Q000494:pharmacology; D002700:Chloramines / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000493:pharmacokinetics; D005978:Glutathione / Q000378:metabolism; D005981:Glutathione Synthase / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D007079:Ileitis / Q000503:physiopathology; D007082:Ileum / Q000187:drug effects / Q000648:ultrastructure*; D066298:In Vitro Techniques; D008657:Metabolic Clearance Rate; D009119:Muscle Contraction / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D011817:Rabbits
D002630:Chemotactic Factors; D002700:Chloramines; C072355:histamine monochloramine; C077644:histamine dichloramine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006632:Histamine; D004492:Edetic Acid; D005981:Glutathione Synthase; D005978:Glutathione