Nonparietal Secretion Research Articles

The effect of prostaglandins on gastric parietal and non-parietal secretion in the anaesthetized rat.

The effects of prostaglandin E2 (PGE2), 16,16-dimethyl prostaglandin E2 (dmPGE2) and prostaglandin F2 alpha (PGF2 alpha) on gastric secretion have been examined in the anaesthetized rat. The prostaglandins stimulated the secretion of a non-parietal juice which was rich in Na+ and Cl- with smaller amounts of K+ and HCO3-. Doses of the prostaglandins that stimulated gastric non-parietal secretion also inhibited histamine stimulated gastric acid secretion, and thus the same rank order of potency was obtained for the prostaglandins on the two secretory mechanisms, viz. dmPGE2 greater than PGE2 greater than PGF2 alpha. During the secretion of endogenous gastric acid the secretagogue effect of the prostaglandins on non-parietal secretion was diminished, and this effect appeared to be due to the presence of intraluminal acid since it was mimicked by application of exogenous HCl to the gastric mucosal surface. Thus, the present results show that prostaglandins affect both the parietal and non-parietal secretions in the rat stomach and that these mechanisms show some interdependence.

Effects of Age on Gastric Alkaline and Nonparietal Fluid Secretion in Humans

Little is known about the effect of age on gastric alkaline and nonparietal secretion. Using a previously validated technique, we prospectively measured gastric HCO^–₃ and nonparietal volume secretion, as well as secretion of H⁺, Na⁺, K⁺, and Cl^–, in 114 healthy human beings over a wide age range (18–82 years). Each subject had normal oxyntic mucosal histology, was on no medication known to affect gastric secretion, and was studied under both basal (fasting) conditions and following stimulation of gastric H⁺ secretion by pentagastrin. There was a significant (p < 0.05) decline in gastric HCO^–₃, Na⁺, and nonparietal fluid secretion with advancing age, but not in H⁺, K⁺, Cl^– or parietal fluid secretion. As a consequence of reduced gastric HCO^–₃ and nonparietal fluid secretion, mean H⁺ concentrations in gastric juice increased significantly with advancing age. Thus, in healthy subjects with normal gastric histology, advancing age was associated with a significant decline in gastric HCO^–₃, Na⁺, and nonparietal fluid secretion, resulting in an increase in gastric acidity (H⁺ concentration).

Effects of Helicobacter pylori gastritis on gastric secretion in healthy human beings.

Helicobacter pylori gastritis is common, but effects on gastric secretion are not well understood. We measured basal and pentagastrin-stimulated gastric acidity, pepsin activity, and fluid output, as well as serum gastrin concentrations and H. pylori antibody levels, before and after treatment of H. pylori gastritis in 28 men and women. Subjects were studied before and 1 and 3 mo after a course of bismuth, metronidazole, and tetracycline. Elimination of H. pylori gastritis, accomplished in 14 subjects, increased basal and pentagastrin-stimulated gastric acidity (by 15 meq/l) and basal acid output significantly (by 2.1 meq/h 1 mo after therapy). Elimination of H. pylori had an opposite effect on pepsin secretion, significantly decreasing pepsin output by 30%. Elimination of H. pylori significantly reduced nonparietal fluid output by 35%, without affecting fluid output from parietal cells. Serum gastrin and H. pylori antibody levels declined significantly after elimination of H. pylori. None of these changes was observed in 14 subjects whose H. pylori gastritis was resistant to antimicrobial therapy. In summary, eradication of H. pylori infection increases gastric acidity by reducing nonparietal gastric secretion from peptic and other cells.

Effects of nizatidine on gastric acid and bicarbonate secretion

The effects of nizatidine on human gastric parietal secretion (volume and acid output) and nonparietal secretion (volume and bicarbonate concentration and secretion) were evaluated in 18 patients with duodenal ulcer. Nizatidine reduced the volume of pentagastrin-stimulated gastric secretion and gastric acid secretion. Nizatidine also decreased the volume of nonparietal secretion and bicarbonate secretion, although bicarbonate concentration remained unchanged.

Gastric HCO3- secretion: relationship with Na+ secretion and effect of acetazolamide in humans

We examined the relationship between gastric HCO3- and Na+ secretion under fasting and sham-fed conditions in nine healthy men and also evaluated the effect of the carbonic anhydrase inhibitor acetazolamide on gastric secretion of HCO3- and Na+. Secretion of H+, K+, and Cl- were also measured. Gastric HCO3- secretion rates under fasting and sham-fed conditions closely paralleled Na+ secretion rates. A maximally tolerated intravenous dose (10 mg/kg) of acetazolamide significantly inhibited H+, Cl- and K+ secretion but did not significantly affect Na+ or HCO3- secretion. Thus the gastric mucosa secretes HCO3- and Na+ in parallel in humans both under fasting and sham-fed conditions. Relative to parietal secretion of HCl, nonparietal secretion of HCO3- and Na+ is resistant to carbonic anhydrase inhibition.

Ionic fluxes induced by topical misoprostol in canine gastric mucosa

We studied the dose response of ionic fluxes in canine chambered gastric segment mucosa to increasing doses of topical misoprostol (0.1, 1, 10, 100, and 1000 micrograms). The fluxes were also correlated with the simultaneous changes in focal gastric mucosal blood flow measured by laser-Doppler flowmetry. After misoprostol administration, there was a dose-dependent increase in focal gastric mucosal blood flow (Emax = 8.23 +/- 3.25 V at 10 micrograms; ED50 = 1.05 micrograms), pH, and the outputs of ions (Na+, K+, Cl-, and HCO3-) and fluid (Emax for pH and fluxes greater than or equal to 1000 micrograms). ED50 values for these outputs ranged from 215.40 to 340 micrograms (mean +/- SE = 279.08 +/- 24.27 micrograms). H+ output showed a dose-dependent decrease to zero at the 10-micrograms dose, the dose at and after which net HCO3- secretion became obvious. The slopes of the dose-response curves for the fluxes of fluid, Na+, K+, Cl-, and HCO3- were significantly different (p less than 0.01) from the slope of the curve for mucosal blood flow changes. There were no correlations between the changes in these fluxes and blood flow changes. Na+ and Cl- were the predominant cation (98.84%) and anion (98.19%), respectively, in the misoprostol-induced secretion. Misoprostol stimulates a composite alkaline gastric nonparietal secretion, predominantly Na+ and Cl-, but also containing K+ and HCO3-. Our results suggest different mechanisms for the effects on nonparietal secretion and focal gastric mucosal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of the stable thromboxane A2-mimetic, U46619, on gastric mucosal damage and gastric non-parietal secretion in the rat.

The effects of the thromboxane A2-mimetic, U46619, and the thromboxane receptor antagonist, AH23848, on ethanol-induced gastric mucosal damage and gastric non-parietal secretion have been examined in the rat. Oral dosing with U46619 or AH23848 produced a dose-related inhibition of ethanol-induced gastric mucosal damage in the conscious rat, and these effects were partially blocked by indomethacin treatment. Intragastric application of U46619 or AH23848 to the stomach of the anaesthetized rat stimulated the gastric secretion of a juice which consisted principally of Na+ and Cl- ions. These secretagogue effects of both compounds were blocked by indomethacin treatment. These results show that U46619 and AH23848 induce secretory and protective effects in the stomach of the rat, although these responses probably do not involve thromboxane receptors and are mediated, at least in part, by endogenous prostaglandins. The results are discussed in relation to the role of endogenous thromboxane A2 in gastric mucosal protection, and of the possible protective function of non-parietal secretion in the stomach.

Simulated meal test. A new method for estimation of parietal and non-parietal secretion in response to food.

In ten healthy volunteers gastric secretion was stimulated by a simulated meal, in which the cephalic phase was activated by modified sham feeding and the gastric phase by repeated instillations and withdrawals of a meat soup. The gastric aspirates were analyzed for acid and pepsin and the outputs quantitated by the recovery of an unabsorbable marker (polyethylene glycol). Instillation of liquid meal without sham feeding produced 58% and 65% of pentagastrin-stimulated secretion of acid and pepsin, respectively. Concomitant sham feeding increased the stimulation further, so that the outputs evoked by the combined stimulus (simulated meal test) were similar to that achieved by the pentagastrin test. The coefficient of variation of duplicate tests was 4.5% for acid and 5.4% for pepsin output. The technique is suitable for measuring both parietal and non-parietal secretion in response to food.

Effect of graded 15(R)15 methyl prostaglandin E2 and of indomethacin on the gastric secretory and plasma gastrin response to modified shamfeeding.

Vagal stimulation by modified shamfeeding in healthy subjects induced about fourfold increases of gastric outputs of acid, chloride, sodium and potassium. Prior oral 15(R)15 methyl prostaglandin E2 inhibited dose-dependently the peak and total gastric acid response to modified shamfeeding by lowering both the secreted volumes and the acidity. The inhibition by 15 micrograms of the analogue exceeded 50% and the suppression was submaximal by 140 micrograms. Gastric output of chlorides decreased in a dose-related way. The hydrogen ion output was proportionally more reduced than the chlorides. The analogue did not affect the gastric output of sodium. Potassium decreased in a dose-related way. Indomethacin was without effect on the gastric acid response to shamfeeding but reduced the sodium output compared to in controls and in series with the analogue. Plasma gastrin was slightly but significantly elevated by the shamfeeding procedure. This elevation was absent or even reversed by 15(R)15 Me PGE2. No effect was recorded by indomethacin pretreatment. Vagal stimulation augments both the parietal and non-parietal components of the gastric secretion. Low doses of oral 15(R)15 Me PGE2 were effective in suppressing the vagally stimulated acid secretion. Neutralization by the gastric non-parietal secretion can contribute to reduce the acid response. Blocking of the prostaglandin biosynthesis decreased gastric sodium output, suggesting indirectly that endogenous prostaglandins may be involved in modulating the gastric non-parietal secretion.

Gastric bicarbonate secretion in humans. Effect of pentagastrin, bethanechol, and 11,16,16-trimethyl prostaglandin E2.

Although the stomach is mainly known for its ability to secrete hydrochloric acid, there is increasing evidence that the gastric mucosa also secretes bicarbonate. A simple method for simultaneous measurement of gastric HCO-3 secretion and H+ secretion was developed from a two-component model of gastric secretion. The method, which is based upon gastric juice volume, H+ concentration, and osmolality, was validated both in vitro and in vivo. In 14 healthy human beings, basal gastric HCO-3 secretion averaged 2.6 mmol/h (range, 0.7-8.7 mmol/h). Basal HCO-3 secretion was approximately 50% of basal H+ secretion and there was a significant correlation between basal HCO-3 and H+ secretion in individual subjects (r = 0.79). HCO-3 was secreted in basal nonparietal secretion at a concentration of approximately 90 mmol/liter. Intravenous pentagastrin infusion markedly stimulated H+ secretion but did not increase HCO-3 secretion. During pentagastrin infusion, the cholinergic agonist, bethanechol, significantly augmented H+ secretion (from 20.2 to 24.7 mmol/h) and increased HCO-3 secretion (from 2.2 to 4.2 mmol/h). A prostaglandin E2 analogue significantly reduced H+ secretion and increased HCO-3 secretion during pentagastrin infusion. The reduction in net gastric juice H+ output following prostaglandin E2 was due more to H+ secretory inhibition than to HCO-3 secretory stimulation. We conclude that the healthy human stomach actively secretes HCO-3 and that gastric HCO-3 secretion can be influenced by cholinergic stimulation and by prostaglandin E2.

Effect of Bethanechol (Urecholine) on Gastric Acid and Nonparietal Secretion in Normal Subjects and Duodenal Ulcer Patients

There is limited information on the effect of cholinergic agonists on gastric acid secretion in humans. In the present study we found that a large intravenous dose of bethanechol (50 µ/kg · h) significantly increased gastric juice output and salivary flow but did not significantly affect gastric acid output or acid concentration in healthy subjects. Gastric juice osmolality decreased significantly during bethanechol infusion, suggesting neutralization of gastric acid by bicarbonate. Assuming that parietal (acid) secretion contains 160 mM of H+ and that nonparietal (alkaline) secretion contains 25 mM of bicarbonate we calculated that bethanechol increased both parietal and nonparietal secretion in each of 6 healthy subjects and also in 9 of 10 patients with duodenal ulcer. Thus the increase in gastric juice output in response to bethanechol was due to stimulation of both acid and alkaline secretion. Parietal secretion during bethanechol infusion averaged 27% ± 4% of maximal pentagastrin-stimulated parietal secretion in healthy subjects and averaged 44% ± 8% of maximal pentagastrin- or histamine-stimulated secretion in duodenal ulcer patients. Unlike bethanechol, neither pentagastrin- nor histaminestimulated nonparietal secretion. Atropine (2.3 µg/ kg) also did not affect basal nonparietal secretion, although this dose of atropine significantly reduced basal parietal (acid) secretion.

A comparison of the effects of prostacyclin and the 15(S), 15-methyl analogs of PGE2 and PGF2-alpha on gastric parietal and nonparietal secretion.

The mechanism by which prostaglandins protect the gastric mucosa is unclear. Although this action has been shown to be independent of the ability to inhibit parietal secretion as measured by hydrogen ion (H+) output, it may be related to stimulation of nonparietal secretion measured here as sodium ion (Na+) output. Five conscious, chair-adapted rhesus monkeys received an infusion of either prostacyclin (PGI2; 125, 175, or 250 ng/kg/min intravenously) or the 15(S), 15-methyl analog of either PGF2α (mePGF2α; 0, 1000, or 2000 ng/kg/min subcutaneously) or PGE2 (mePGE2; 0, 15, or 30 ng/ke/min subcutaneously) on different days. The output of H+, Na+ potassium (K+), and chloride (Cl−) ion were determined using a dye dilution technique during a basal period and following the intragastric administration of an 80-ml water load. PGI2 (175 and 250 ng/kg/min), mePGF2α, and mePGF2 all significantly inhibited H+ output. Both basal and postload Na+ output were increased significantly by mePGE2, while only postload Na+ output was significantly enhanced by mePGF2α. Na+ output was not modified by PGI2. K+ output was unchanged by mePGE2α or mePGF2α; however, postload K+ output was significantly inhibited by the highest dose of PGI2. Both basal and postload Cl− output were suppressed significantly by PGI2 while basal Cl− output was decreased significantly by the higher dose of mePGF2α and postload Cl− output was inhibited by both doses of mePGF2α. In contrast, Cl− secretion was unaffected by mePGE2. Thus, mePGE2 markedly increased nonparietal secretion, while mePGF2α mildly increased and PGI2 did not affect nonparietal secretion. On the basis of these results, a stimulation of nonparietal secretion cannot be considered as the common mechanism for the gastric cytoprotective effect of these prostaglandins.

Prostaglandins alter the relationship between gastric hydrogen ion concentration and flow: evidence for stimulation of non-parietal secretion in the cat.

1. The effect of i.v. administration of prostaglandin (PG) E(2) (10-40 mug kg(-1) h(-1)), 16,16-dimethyl PGE(2) (0.1-0.5 mug kg(-1) h(-1)), PGE(1) (16-20 mug kg(-1) h(-1)), PGA(1) (5-11 mug kg(-1) h(-1)) and PGF(2alpha) (40 mug kg(-1) h(-1)) on the relationship between [H(+)] and flow of gastric juice during stimulation of gastric secretion by pentagastrin was investigated in conscious cats prepared with cannulated gastric fistulae.2. A- and E-type prostaglandins significantly reduced pentagastrin-stimulated acid output. This inhibition was associated with a reduction of the [H(+)] of the gastric juice such that the [H(+)] observed at any flow rate tended to be lower than the normal range observed with pentagastrin alone. With the highest doses of these prostaglandins the mean [H(+)] values were well below the normal range with pentagastrin alone.3. At the dose tested, PGF(2alpha) had little effect on acid output, and did not alter the relationship between [H(+)] and gastric flow.4. There is a linear relationship between acid output and gastric flow and this relationship is similar during stimulation of gastric secretion by pentagastrin, histamine or insulin. Gastric acid inhibitory doses of cimetidine, atropine and somatostatin did not alter this relationship. In contrast the A- and E-type prostaglandins displaced this relationship to the right of the normal line observed with the acid stimulants alone. A- and E-type prostaglandins reduced the slope of the line relating acid output and gastric flow from approximately 150-170 muequiv/ml(-1) to approximately 100-120 muequiv ml(-1), this being taken as evidence of dilution of the parietal H(+) secretion with a non-parietal secretion.5. The volume of non-parietal gastric secretion was calculated as the gastric flow at zero acid output by extrapolation of linear plots of acid output versus gastric flow. Unstimulated gastric flow measured directly was 0.75 ml 15 min(-1). The calculated non-parietal flow was in the range 0.52-0.90 ml 15 min(-1) during stimulation of gastric secretion with pentagastrin, histamine and insulin, and inhibition of pentagastrin-stimulated acid secretion with cimetidine, atropine and somatostatin. PGE(2) (1.51 ml 15 min(-1)) and 16,16-dimethyl PGE(2) (1.20 ml 15 min(-1)) nearly doubled the calculated non-parietal flow.6. These data demonstrate that gastric acid inhibitory doses of A- and E-type prostaglandins can reduce the [H(+)] in the bulk fluid of the gastric lumen during stimulation of acid secretion. The data provide evidence that these prostaglandins stimulate a non-parietal component of gastric secretion. This might be gastric bicarbonate and mucus secretion.

Stimulation of non-parietal cell secretion in canine Heidenhain pouches by 16,16-dimethyl prostaglandin E2.

The permeability effects of topical and intravenous prostaglandin E2 (PGE2) and 16,16-dimethyl prostaglandin E2 (16DM) were studied in canine Heidenhain pouches using an acid-free perfusate, and changes in volume and HCO-3 content of the perfusate were measured. Topical and intravenous 16DM increased the apparent flux of Na+ and Cl-, and stimulated the secretion of fluid containing HCO-3. 16DM stimulates non-parietal cell secretion and therefore the movement of Na+ cannot be interpreted as passive flux in response to changes in permeability.

Exchange diffusion in acid-filled gastric pouches

The reduction of acidity in acid-filled innervated and denervated canine, gastric pouches increased with increasing concentrations of HCl within the lumen. This increasing acidity reduction occurred without an increase in volume, which could be attributed to a non-parietal alkaline secretion entering the lumen. The increasing acidity reduction was not accompanied by an increased entry of chloride ions as would occur if the acidity reduction were due to the entry of a theoretical non-parietal alkaline secretion having the composition of interstitial fluid. The acidity reduction in acid-filled gastric pouches was inversely proportional to and numerically equal to the sodium ion gain of an acid-filled pouch. The results indicate that acidity reduction is due to exchange diffusion, intraluminal hydrogen ions leaving for interstitial sodium, and that the alkaline non-parietal secretion, if present at all, contributes negligibly to acidity reduction in an acid-filled gastric pouch.

Histamine Secretory Tests in Cats: An Evaluation of Results Based Upon Hollander's Two-Component Theory

Summary A method is described of performing acute total gastric pouch secretory studies in anesthetized cats. The maximal secretory capacity of the gastric epithelium in these preparations was influenced by the duration of histamine administration as well as the dose. It is possible to obtain a larger output of gastric juice for a short period by doubling the dose of histamine each 2 hours than by giving a larger dose over a prolonged test. The correlations between the ionic concentrations in the stimulated and in the unstimulated cats are on the whole consistent with Hollander's two-component theory of gastric secretion. The composition of the two components differs in the two states, the chief difference being an increase in the K concentration in the nonparietal cell secretion on stimulation, with a corresponding decrease in the K in the parietal cell secretion. Histamine increases the rates of both secretions with a greater increase in the parietal cell secretion. The reason for the K content of parietal secretion, which is at variance with the Hollander theory, is not clear but may be due to species difference, to retained innervation of the stomach or to the anesthetic.