Alkali Secretion Research Articles

Effect of bismuth subcitrate and sucralfate on rat duodenal and human gastric bicarbonate secretion in vivo.

Acid and alkali secretion have been examined together with prostaglandin E2 production in response to two mucosal protective drugs, colloidal bismuth subcitrate and sucralfate. Doses of colloidal bismuth subcitrate in the therapeutic range (120 and 1200 mg) had no effect on alkali secretion or luminal PGE2 output when perfused into the stomach of human volunteers. Similarly, in the anaesthetised rat, neither gastric acid nor duodenal alkali secretions were influenced by iv (12 mg/kg) or topical (120 mg/ml) administration of colloidal bismuth subcitrate. In contrast, perfusion of the human stomach with 1 g sucralfate stimulated bicarbonate output by 50%, a response which was unaffected by indomethacin (25 mg/h). A rise of 64% in gastric PGE2 output after sucralfate was, however, prevented by indomethacin pretreatment. Alkali secretion by rat duodenum was also increased by sucralfate but the response depended on the basal secretory rate. Low basal secretors (less than 3 mumol) showed a 75% stimulation whereas rats with high basal secretory rates (greater than 3 mumol) showed no significant response. All duodenal preparations regardless of basal secretory rate showed a stimulation of bicarbonate output with topical PGE2. The results suggest that enhancement of gastroduodenal bicarbonate secretion may play a role in the protective action of sucralfate but is unlikely to explain mucosal protection by colloidal bismuth subcitrate.

Acid and Alkali Secretion by the Turtle Urinary Bladder

Annals of the New York Academy of SciencesVolume 574, Issue 1 p. 463-479 Acid and Alkali Secretion by the Turtle Urinary Bladder A Model System for Neurohormonal Regulation of Acid-Base Homeostasis WILLIAM A. BRODSKY, WILLIAM A. BRODSKY Department of Physiology and Biophysics Mt. Sinai School of Medicine New York, New York 10029Search for more papers by this author WILLIAM A. BRODSKY, WILLIAM A. BRODSKY Department of Physiology and Biophysics Mt. Sinai School of Medicine New York, New York 10029Search for more papers by this author First published: December 1989 https://doi.org/10.1111/j.1749-6632.1989.tb25184.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume574, Issue1Bicarbonate, Chloride, and Proton Transport SystemsDecember 1989Pages 463-479 RelatedInformation

Effect of the luminal hydrogen ion on alkali and mucus secretion in the rat stomach.

This study was designed to investigate the effect of luminal H+ on alkali and mucus secretion in the isolated rat stomach. At various luminal pHs, the thickness and the pH gradient of the mucus gel layer were measured. The maximum pH and calculated alkali secretion showed that the latter was stimulated in parallel with an increase in luminal H+ concentration, especially when the luminal pH became less than 3.5. Mucus secretion, however, was not significantly affected by the luminal H+ concentration. These results suggest that alkali and mucus secretion in the stomach are not regulated by the same mechanism, but different ones.

In vitro measurement of the pH gradient and thickness of the duodenal mucus gel layer in rats.

The mucus bicarbonate barrier of the duodenum has lately been reported to be one of the most important defensive factors for the duodenal mucosa. We established an in vitro system for evaluating the mucus bicarbonate barrier in the rat duodenum. Our method allows direct measurement of the pH gradient as well as the thickness of the mucus gel layer of the rat duodenum in vitro. The obtained results suggest that alkali secretion in response to acid-loading as well as the thickness of the duodenal mucus gel layer are greater than those in the stomach.

Neural regulation of duodenal alkali secretion: effects of electrical field stimulation.

The role of transmitters released from enteric neurons in regulating bicarbonate secretion by the proximal duodenum has been studied using electrical field stimulation (EFS). Stripped duodenal mucosa from Rana catesbeiana was mounted as an intact tube over circular platinum electrodes, and luminal alkalinization was measured by pH stat titration before, during, and after EFS. Transmucosal potential difference (PD) was simultaneously measured before and after EFS by paired electrodes. Square-wave pulses 50 V, 2 ms in duration, at 10 Hz were delivered in trains of 0.5 s at 1 Hz for periods of 15 min after stable basal secretion. This resulted in a 63 +/- 27% increase in alkalinization that returned to basal values after cessation of the stimulus, without change in transmucosal PD. Serosal-to-lumen [3H]mannitol flux was not affected. Repetition of the stimulus resulted in similar responses for as long as the tissue remained viable. The response to EFS was abolished by tetrodotoxin (10(-6) M) and veratrine (0.1 mg/ml), indicating that intrinsic neurons were responsible for mediating the effect. In addition, the effect was blocked by serosal dinitrophenol (10(-4) M), indicating that the secretory response occurred by a metabolically dependent process. These results indicate that alkalinization by proximal duodenum may be controlled by neurotransmitter release from local enteric neurons.

Vasoactive intestinal peptide stimulates alkali excretion in turtle urinary bladder

The turtle urinary bladder possesses an active transport mechanism for the electrogenic secretion of alkali. This process is independent of exogenous Cl and Na, induced by cyclic AMP (cAMP), and potentiated in bladders from NaHCO3-loaded (alkalotic) turtles. In the present study, it is shown that the serosal addition of vasoactive intestinal peptide (VIP) induces rapidly developing parallel increases in alkali secretion and in the short-circuiting current carried by this secretion. The VIP-induced increment in alkali secretion is greater in the presence than in the absence of an exogenously added phosphodiesterase inhibitor. Additions of a cAMP analog subsequent to the VIP-induced alkali secretion fail to induce any further increase in alkalinization. These results provide evidence for the action of VIP as a hormonal up regulator of alkali excretion in the turtle urinary bladder.

HCO3- secretion in rat duodenum after treatment with omeprazole and ranitidine.

The bicarbonate secretion by the duodenal mucosa, which is stimulated by luminal acid, is very probably important in mucosal protection against the acid. It was of interest to investigate whether long-term deprivation of the mucosa of this acid stimulus affected the alkali secretion. Sprague-Dawley rats were treated for 4-6 weeks with either omeprazole, 14 mg/kg body weight twice daily, or ranitidine, 300 mg/kg twice daily, by means of gastric intubation. The rate of bicarbonate secretion by the duodenal mucosa was determined in situ by continuous titration. Neither the basal secretion nor the increase in secretion in response to stimulation by prostaglandin E2 or luminal acid (pH 2.0 for 5 or 60 min) differed in treated animals from that in controls that had received placebo (p greater than 0.05). Thus, 4-6 weeks of treatment with omeprazole or ranitidine did not reduce duodenal mucosal bicarbonate secretion in the rat, nor did these drugs diminish the ability of this mucosa to respond to prolonged luminal acidification or luminally administered prostaglandin E2.

Influence of opiates on alkali secretion by amphibian gastric and duodenal mucosa in vitro

Experiments were performed to study the effects of opiates on gastric and duodenal alkali secretion in amphibian mucosa in vitro. Alkali secretion by fundic mucosa of Rana temporaria, or antral mucosa of Rana catesbeiana, was unaffected by morphine, methionine-enkephalin and leucine-enkephalin, two enkephalin analogues, or the opiate antagonist naloxone. Acid secretion by fundic mucosa in vitro was not influenced by 10−5 and 10−4 M morphine, or by 10−7 to 10−5 M naloxone. However, duodenal alkali secretion in Rana catesbeiana was stimulated by opiates while the electrical potential difference was unaffected. Morphine stimulated secretion, maximally at 10−5 M, by 33% over basal values, 30 min after exposure to the drug, whereas the maximal response to methionine-enkephalin occurred at 10−6 M and was obvious within the first 15 min after administration. The effects of these opiates were prevented by pretreatment with naloxone or with the more specific opiate receptor antagonist ICI 154129. The response to morphine was inhibited when bicarbonate in the nutrient-side solution was replaced by the impermeant anion HEPES or by removal of chloride from the bathing media. Furosemide (10−3 M) also inhibited the response of duodenal mucosa to morphine. The nerve-blocker tetrodotoxin (10−7 M) prevented the morphine-induced response. These data suggest that opiates can stimulate duodenal alkali secretion, probably by activating an electrically neutral Cl−/HCO3− exchange. It seems likely that the effect of opiates is mediated by a neurologic intermediary, and the results suggest the possibility that duodenal alkali secretion may be under some neurologic control.

Effect of certain ulcer-healing agents on amphibian gastroduodenal bicarbonate secretion.

The effect of luminal application of aluminum sulphate, sucralfate, and bismuth subcitrate on gastroduodenal alkali secretion has been studied with isolated amphibian mucosa. The mucosa, stripped of its external muscle layer, was mounted in chambers that allowed titration of alkali secretion and measurement of transmucosal potential difference and electrical resistance. Neutral aluminum sulphate (3 X 10(-3) M) increased bicarbonate secretion by fundic (mean +/- SEM = 144 +/- 48%, n = 5, P less than 0.05), antral (mean +/- SEM = 214 +/- 63%, n = 4, P less than 0.05), and duodenal (mean +/- SEM = 133 +/- 44%, n = 6, P less than 0.005) mucosa. Sucralfate (0.5 g/l) stimulated fundic (mean +/- SEM = 183 +/- 87%, n = 4, P less than 0.05) and antral (mean +/- SEM = 156 +/- 58%, n = 5, P less than 0.005) alkali secretion and, at a concentration of 1 g/l, duodenal output (mean +/- SEM = 42 +/- 15%, n = 6, P less than 0.05). Bismuth subcitrate (10(-4) M) produced a significant rise in fundic (mean +/- SEM = 80 +/- 21%, n = 5, P less than 0.05) and duodenal (mean +/- SEM = 62 +/- 7%, n = 6, P less than 0.05) alkali secretion. None of these agents altered transmucosal potential difference or electrical resistance. The actions of these agents on gastroduodenal bicarbonate secretion may be important in their ulcer healing effects.

The “divided stomach”—A model for separate acid and alkali collection in the pig

Bile duct ligation (BDL) in the pig results uniformly in fatal oesophago-gastric ulceration which appears to be related to hypersecretion of acid. The presence of bile in normal porcine gastric juice may interfere with studies of acid secretion. The present studies were conducted in pigs with the stomach divided into two separate pouches (proximal and antral) which allowed individual collection of acid or alkali secretion. In normal pigs, division of the stomach resulted in a 30–50% decrease in secretion, rather than any increase in measureable acid. In BDL pigs, there was an 8- to 15-fold increase in alkali collection by antral pouches which may have been in response to acid hypersecretion, or merely duodenal or pancreatic juice reflux. No normal pigs with divided stomachs developed significant ulceration suggesting that such ulcers were not related to exclusion of bile from the stomach. It is proposed that a total gastric fistula may be used in the pig for studies of acid secretion, and that the model with divided stomach may be used for assessment of the effects of secretagogues or hormones upon individual acid or alkali secretion.

Gastric mucosal defence mechanisms.

Gastric mucosa has a particular ability to resist acid/peptic digestion. The nature of the presumed barrier to acid and pepsin has been elusive but recent work suggests that a combination of mechanisms is likely to be involved. Amongst these the mucus gel layer combined with secretion of alkali by the surface epithelium is likely to form a first line defence. The demonstration of a pH gradient within the mucus gel layer supports such a hypothesis. Agents which damage the mucosa such as aspirin and bile salts inhibit the maintenance of the pH gradient allowing the luminal surface of the epithelium to become more acid. Prostaglandins enhance this pH gradient, an observation which may be relevant to the protective properties of prostaglandins. This alkaline zone can be compromised by high levels of luminal acidity and it thus has a limited capacity to prevent acid reaching the mucosa. The local microcirculation is of importance in maintaining surface epithelial metabolic integrity and interstitial fluid bicarbonate may be important in neutralising any acid which may reach the subepithelial layers. This may in part explain the ability of an actively secreting gastric epithelium to resist damage to a greater extent than a resting mucosa. Recent exciting work has focussed on the ability of gastric epithelium to reform by a process which has been termed restitution, after acute mucosal damage. This process appears to be rapid and occurs within an hour or so. Repeated rapid repair may be a common occurrence in the maintenance of mucosal integrity. Finally, it has been proposed that a hydrophobic property of surface epithelium in the stomach may be relevant to mucosal protection.

3 - Gastroduodenal Defence Mechanisms

In the healthy stomach and duodenum aggressive factors such as luminal acid and pepsin are balanced by defence and repair processes. In recent years components of the mucosal defences which have been identified include the layer of mucus gel adherent to the surface of these mucosae, surface epithelial alkali secretion, mucosal blood flow and the supply of bicarbonate to the surface epithelium as well as the processes involved in rapid mucosal repair. Secretion of alkali maintains the pH within the mucus gel on the epithelial cell surface at neutrality, in spite of luminal pHs as low as 1.5 to 2.0. Alkali secretion is stimulated up to ten-fold by luminal acid. This response is mediated by endogenous production of prostaglandins, humoral factors and, possibly, by nervous mechanisms. Impairment of the response results in mucosal ulceration. The mucus layer (approximately 200 micron deep in man) provides an unstirred zone at the mucosal surface in which diffusing is delayed, allowing time for secreted HCO-3 to neutralize acid diffusing toward the mucosa. In addition mucus is impermeable to pepsin. During secretion of H+ ions, HCO-3 is produced, and secreted by the surface epithelium. Stimulation of acid secretion increases the ability of gastric mucosa to resist acid and pepsin, presumably by providing more HCO-3. Parenteral HCO-3 (but not other buffer species) provides similar protection to both the gastric and duodenal mucosae. The remarkably rapid reconstitution of the surface epithelium, within 30 minutes after acute superficial damage, is clearly an important 'defence' mechanism. Studies of the control of these defence and repair mechanisms should provide a greater understanding of common gastroduodenal diseases.

Chloride-induced increment in short-circuiting current of the turtle bladder. Effects of in-vivo acid-base state

Evidence for the participation of conductive and non-conductive (exchange) transmembrane anion pathways in the luminal acidification, alkalinization, and chloride-reabsorptive functions of the turtle bladder is provided from the pattern of Cl −-induced changes in transepithelial electrical parameters of isolated urinary bladders from three groups of donor turtles: control or post-absorptive turtles (those killed 5 days after feeding); acidotic turtles (NH 4Cl-loaded); and alkalotic turtles (NaHCO 3-loaded). The predominance of each of the three aforementioned transport functions as well as the response to Cl −-addition is altered by the in-vivo electrolyte balance of the turtle. In post-absorptive bladders, which are poised for acidification and Cl − reabsorption, the mucosal and serosal addition of Cl − to Na +-free, (HCO 3 − + CO 2)-containing media increases the negative short-circuiting current ( I sc ). In acidotic bladders, which are poised for acidification but not Cl − reabsorption, mucosal Cl − addition has no effect on this I sc whereas serosal Cl − addition increases the negative I sc in a manner identical to that observed in the post-absorptive bladders. Alkalotic bladders do not possess an acidification function but instead are poised for Cl − reabsorption and cAMP-dependent electrogenic alkali secretion (positive I sc ). In these bladders, serosal Cl − addition is without effect while mucosal Cl − addition produces transient changes in this positive I sc . It is found that these results can be replicated by a model of the turtle bladder in which transmembrane Cl − and HCO 3 − conductive and exchange paths mediate transepithelial acidification, alkalinization and Cl − reabsorption.

Simultaneous measurement of gastric acid and duodenal alkali secretion by in situ titration in health and disease.

We have devised a technique for simultaneously measuring the acid secretion into the stomach and alkali into the duodenum by in situ titration using a modification of the technique of Fordtran and Walsh. Using this technique, the results of acid and alkali secretion measured simultaneously were identical with those obtained using the conventional aspiration method on separate days. In response to stimulation with pentagastrin acid output was 17.2 +/- 1.4 vs 15.4 +/- 1.9 mmol/h and alkali response with secretin was 16.0 +/- 0.8 vs 14.4 +/- 1.5 mmol/h. The response to food was measured in 10 control subjects, 10 patients with duodenal ulcer, and 10 patients with pancreatitis. In controls, the acid and alkaline secretion were similar (15.8 +/- 1.7 vs 18.2 +/- 1.3 mmol/h), in patients with duodenal ulcer acid secretion was significantly greater than alkaline secretion (31.9 +/- 2.2 vs 21.9 +/- 1.7 mmol/h), and in patients with pancreatitis the alkali secretion was significantly less than acid (19.8 +/- 1.9 mmol/h acid vs 11.4 +/- 0.6 mmol/h alkali). It can, therefore, be concluded that in response to food the patients with duodenal ulcer are significant hypersecretors of acid (DU acid greater than DU alkali output) and patients with pancreatitis are significant hyposecretors of alkali (pancreatitis-alkaline output less than acid output) and normal subjects secrete equal amounts of acid and alkali.

Effects of non-steroidal anti-inflammatory drugs and prostaglandins on alkali secretion by rabbit gastric fundus in vitro.

The effects of non-steroidal anti-inflammatory drugs and prostaglandins E(2) and F(2alpha) on the secretory and electrical activity of isolated rabbit fundic mucosa have been studied. Spontaneous acid secretion was inhibited by serosal side application of sodium thiocyanate (6x10(-2)M) and the resulting alkali secretion measured by pH stat tiration. Serosal side application of indomethacin (10(-5)M) or aspirin (3x10(-3)M) inhibited alkali secretion (0.55+/-0.06 to 0.12+/-0.06 mumol/cm(2)/h, n=6, p<0.01 and 0.28+/-0.06 to 0.11+/-0.03 mumol/cm(2)/h, n=7, p<0.02 respectively). Mucosal or serosal side prostaglandin E(2) (10(-5) to 10(-10)M) and F(2alpha) (10(-4) to 10(-10)M) failed to alter the rate of alkalinisation but secretion was significantly increased by serosal side 16,16-dimethyl-prostaglandin E(2) (10(-6)M) (0.90+/-0.20 to 1.50+/-0.30 mumol/cm(2)/h, n=6, p<0.01). Serosal side application of 10(-6)M prostaglandin E(2) to fundic mucosae pretreated with either aspirin (5x10(-3)M) or indomethacin (10(-5)M), to reduce endogenous E(2) formation, also failed to alter alkali secretion. Pretreatment of the mucosa with 16,16-dimethyl-E(2) (10(-6)M) abolished the inhibitory effect of indomethacin (10(-5)M) on alkali secretion (n=6) but did not modify the secretory response to aspirin (3x10(-3)M) (fall in alkali secretion with aspirin = 81+/-11% and with aspirin plus 16,16-dimethyl-E(2) = 72+/-10%, n=7). In the doses used, none of the prostaglandins or non-steroidal anti-inflammatory drugs altered transmucosal potential difference or electrical resistance. These results show that the damaging agents, aspirin and indomethacin, both inhibit gastric alkali secretion but that modes of action may differ. The observation that prostaglandins, E(2) and F(2alpha) failed to increase alkali production suggests that their protective activity against a variety of damaging agents as shown by others, may be mediated by another mechanism.

Localization of ouabain-binding sites in frog gastric mucosa.

Autoradiography at the light microscopic level was used to localize sites of [3H]ouabain binding in isolated stimulated frog gastric mucosa. Silver grains denoting binding were located near basal and lateral surfaces in both oxyntic and surface epithelial cells. Binding to oxyntic cells occurred well before inhibition of acid secretion, consistent with the view that inhibition by this drug is indirect, and subsequent to inactivation of oxyntic cell Na+-K+-ATPase and the resulting depression of cellular K+. The presence of Na+-K+-ATPase in surface cells, as shown by binding of labeled ouabain, suggests a role for that transport enzyme in electrical activity and secretion of alkali by these cells.

Studies of Acid and Alkaline Secretion by Rabbit Gastric Fundus In Vitro: Effect of Low Concentrations of Sodium Taurocholate

The effect of low concentrations of sodium taurocholate on the secretory and electrical activity of isolated rabbit fundic mucosa has been studied. Fundic mucosa maintained a stable potential difference (10.2 +/- 0.6 mV, n = 70) and electrical resistance (85 +/- 6 omega . cm-2, n = 70) and the majority of preparations spontaneously secreted acid (2.85 +/- 0.31 mumol . cm-2 . h-1, n = 70). Histamine (10(-5) and 10(-4) M) and carbachol (10-4 M) increased acid secretion, and these responses were prevented by cimetidine (10(-3) M) and atropine (10(-5) M), respectively. Mucosal application of taurocholate (10(-4) and 10(-3) M) increased net acidity without altering electrical activity. This response exhibited tachyphylaxis, was not altered by pretreating the tissues with cimetidine (10(-3) M), atropine (10(-5) M), or somatostatin (10(-6) M), and occurred in mucosas maximally stimulated by histamine. Sodium thiocyanate (6 x 10(-2) M, serosal side) inhibited spontaneous acid secretion revealing net alkalinization (0.83 +/- 0.05 mumol . cm-2 . h-1, n = 58) that was completely inhibited by anoxia and potassium cyanide (10(-2) M) and markedly reduced by 2,4-dinitrophenol (10(-4) M). Some fundic preparations spontaneously secreted alkali (1.20 +/- 0.20 mumol . cm-2 . h-1, n = 6) after an initial period of acid secretion. Mucosal-side taurocholate (10(-3) M) converted net alkali secretion by both thiocyanate-treated and spontaneously-secreting mucosas to acid secretion without affecting electrical conductance. These secretory responses may be implicated in the pathogenesis of gastric mucosal damage by bile salts.

Mechanisms of histamine stimulated secretion in rabbit ileal mucosa.

Histamine is present in high concentrations in the intestine and we investigated the possibility that it might have a role here in intestinal transport. When added to the basal side of rabbit ileal mucosa in vitro histamine (10(-4)M) induced a short-lived increase in electrical potential difference and short circuit current. It inhibited net chloride absorption but did not influence sodium transport. Alkali secretion, measured by a pH stat technique, was inhibited, suggesting that bicarbonate secretion was reduced. Both the electrical and ion flux responses to histamine were blocked by the H1 receptor blocker diphenhydramine, but not by the H2 receptor blocker cimetidine. The presence of specific H1 histamine receptors was further supported by shifts in the dose-response curve to histamine by four different concentrations of diphenhydramine. Calculation of a pA2 value from these "Schild' plots provided a figure of 7.85, which is similar to that for H1 receptors in other tissues. Aminoguanidine, a histaminase blocker, had no electrical effects alone but shifted the histamine dose response curve to the left. These studies indicate that histamine inhibits chloride absorption and alkali secretion, possibly by influencing a chloride/bicarbonate exchange process, through specific mucosal H1 receptors. Enhancement of histamine effects by a histaminase inhibitor suggests that histaminases are present in the intestinal mucosa and supports the possibility of a role for endogenous histamine in influencing ion transport. The observations indicate a mechanism by which absorption might be impaired in diseases in which histamine is liberated locally in the intestine.

Effects of histamine receptor antagonists on alkali secretion by ileum

Although the effects of H 1 and H 2 receptor antagonists on the gastric mucosa have been studied extensively, little is known about the effects of such antagonists on the small intestinal mucosa. The present study examines the effects of histamine, pyrilamine (H 1), and cimetidine (H 2) on alkali secretion by the ileum of rabbits. Either HCO 3-containing (25 mmole/liter) or HCO 3-free saline solution (37°C) was perfused continuously through a 10-cm loop of terminal ileum. In the absence and presence of a major HCO 3 concentration gradient across the mucosa, alkali secretion in the absence of histamine or H 1 or H 2 receptor antagonists did not change significantly over a 180-min interval. Neither histamine nor cimetidine significantly altered alkali secretion. However, pyrilamine caused a significant reduction in alkali secretion in both the absence and the presence of a major HCO 3 gradient across the mucosa. The data suggest that endogenous stores of histamine play an important role in the active secretion of HCO 3 by ileal mucosa. This process appears to be associated with H 1 receptors.

Effects of Histamine Receptor Antagonists on Ion Transport by Isolated Ileum of the Rabbit

In contrast to gastric mucosa, little is known about the effects of histamine on small intestinal mucosa. This study examines some of the effects of histamine and its antagonists on ion transport by isolated ileal mucosa. Histamine causes a transient increase in short-circuit current which is blocked by H 1 , but not by H 2 receptor antagonists. H 1 receptor antagonists cause a marked decrease in short-circuit current which is not associated with a significant change in net Na and Cl transport. Since H 1 receptor antagonists reduce the residual ion flux to a negligible value, the effects of histamine antagonists on alkali secretion were measured. Isolated ileal mucosa of the rabbit has two components of alkali secretion. The major component requires HCO 3 on the serosal side of the mucosa, whereas the minor component originates from the mucosa itself. H 1 receptor antagonists inhibit both components of alkali secretion. The effects of H 2 receptor antagonists appear to be qualitatively similar to H 1 receptor antagonists, but the effects of H 2 receptor antagonists are transient. Assuming specificity of histamine receptor antagonists in the concentrations used, the data suggest that tissue stores of histamine in the ileum may play a fundamental role in regulating alkali secretion, which is inhibited by antihistamines of the H 1 type.