Regional differences in the response to platelet-activating factor in rabbit colon.
1. Platelet-activating factor is an inflammatory mediator related to eicosanoids which is known to stimulate anion secretion in the distal colon. Since there are regional differences in ion transport within the colon, the influence of platelet-activating factors on ion transport and epithelial permeability has been studied in rabbit caecum and distal colon mounted in Ussing chambers. 2. The effect of platelet-activating factor (1-50 nmol/l) on net electrogenic ion transport was to stimulate a biphasic increase in short-circuit current in the distal colon but not in the caecum. The platelet-activating factor-induced rise in short-circuit current was shown by ion replacement and pharmacological inhibitor studies to be consistent with chloride and bicarbonate secretion in the early phase, but with chloride secretion alone in the later phase. The effect on ion transport was specific and reversible and was enhanced by 0.25% BSA. 3. Colonic permeability, assessed by transmucosal resistance and mannitol flux, was increased by platelet-activating factor in both the distal colon and the caecum. This was consistent with an effect on platelet-activating factor on the paracellular pathway, because resistance decreased even when transcellular chloride transport was inhibited by frusemide or ion replacement. A specific platelet-activating factor antagonist (U66985) inhibited the effects of platelet-activating factor in both the distal colon and the caecum. 4. The results show that platelet-activating factor stimulates anion secretion only in the distal colon, but increases permeability in both the caecum and the distal colon.
Travis
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SP
Gastroenterology Unit, Radcliffe Infirmary, Oxford, U.K.
Jewell
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DP
D000818:Animals; D002432:Cecum / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity / Q000187:drug effects; D005665:Furosemide / Q000494:pharmacology; D066298:In Vitro Techniques; D008353:Mannitol / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D013997:Time Factors
D002712:Chlorides; D010972:Platelet Activating Factor; D008353:Mannitol; D005665:Furosemide; D012964:Sodium