Mechanisms of acid disposal and acid-stimulated alkaline secretion by gastroduodenal mucosa.
This paper investigates acid disposal by gastric and duodenal mucosa with particular reference to the mechanisms of acid-stimulated luminal alkalinization in the duodenum. The bulk of solute flux across duodenal epithelium occurs by paracellular permeation, and passive diffusion of HCO3 via shunt pathways contributes substantially to luminal alkalinization by this tissue in vitro. Effects on epithelial permeability of two treatments which stimulate mucosal alkaline secretion (PGE2 and low luminal pH) were studied in vivo by measuring transmucosal fluxes of radiolabeled urea (mol wt 76) and inulin (mol wt approximately 5000). Rats were anesthetized and rates of alkalinization in segments of distal duodenum perfused with saline were monitored by continuous titration. PGE2 (10 microM, topically) increased alkaline secretion from 1.63 +/- 0.34 to 3.07 +/- 0.54 microeq/cm/hr (mean +/- SEM, N = 5). Luminal acid exposure (10 mM HCl for 10 min) increased alkalinization rate from 1.54 +/- 0.43 to 2.69 +/- 0.76; subsequent addition of PGE2 induced a further rise to 3.27 +/- 0.54. Recovery of inulin in the luminal perfusate following intravenous injection was less than 10% of that of urea. Topical PGE2 had little or no effect on recovery of either marker. Luminal acidification increased the rate of appearance of urea by 130 +/- 30% (P less than 0.01, N = 6); recovery of inulin rose slightly but did not achieve statistical significance compared with control. Thus stimulation of mucosal alkaline secretion by luminal PGE2 or acid are associated with differential effects on mucosal permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
Bioscience Department, ICI Pharmaceuticals Division, Alderley Park, Macclesfield, Chesire, U.K.
J M
JM
Wilkes
A
A
Garner
T J
TJ
Peters
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D015232:Dinoprostone; D004386:Duodenum / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005744:Gastric Acid / Q000502:physiology*; D005753:Gastric Mucosa / Q000378:metabolism / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism / Q000502:physiology*; D007444:Inulin / Q000378:metabolism; D010539:Permeability; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014508:Urea / Q000378:metabolism
D001639:Bicarbonates; D011458:Prostaglandins E; D014508:Urea; D007444:Inulin; D015232:Dinoprostone