Duodenal Alkaline Research Articles

Contrasting the effects of phytase and pure myo-inositol on the performance, digestibility, blood and egg yolk inositol levels and digestion physiology of laying hens

ABSRACT 1. An experiment was designed to compare the effects of supplementing laying hen diets with phytase and myo-inositol (inositol). 2. Five diets were formulated: high balanced protein (HBP – 840 mg of Dlys/hen/day), HBP with inositol (HBP+I – 0.16%), reduced balance protein (RBP – 672 mg of Dlys/hen/day), RBP with inositol (RBP+I – 0.16%) and RBP with phytase (RBP+P – 3000 FTU/kg). 3. Laying hen production, inositol concentrations, digestive tract morphology, amino acid digestibility and intestinal inositol transporters transcript abundance were evaluated. Data were analysed with a one-way ANOVA in SAS 9.4. Contrasts were used to assess the effect of protein, inositol, phytase and phytase vs. inositol. Differences were accepted when P ≤ 0.05. 4. No effect on hen-day egg production or feed efficiency was found. However, feed intake and the incidence of abnormally shaped eggs were 0.77 g/h/d and 0.17% higher, respectively, in inositol treatments. Inositol decreased egg specific gravity from 1.088 to 1.0865. 5. Inositol concentration in egg yolk was similar among HBP+I, RBP+I and RBP+P, and higher than for the HBP and RBP diet groups. Both gizzard and ileal digesta were enriched in inositol in all supplemented treatments, and phytase supplementation decreased the level of IP5 and IP6 in the gizzard and ileum. Generally, neither phytase or inositol affected amino acid digestibility. 6. Inositol increased transcript abundance of alkaline phosphatase in the ileum, while phytase upregulated duodenal alkaline phosphatase and SMIT1, jejunal SMIT2 and reduced ileal HMIT and SMIT1 abundance. 7. In conclusion, no effect of phytase or inositol was found for laying hen production performance or amino acid digestibility, but egg quality was reduced by inositol supplementation. Inositol concentration in egg yolk was similar among supplemented treatments.

Effect of pectin feeding on obesity development and duodenal alkaline phosphatase activity in Sprague-Dawley rats fed with high-fat/high-energy diet.

Purpose The objective of this study was to evaluate whether pectin feeding would affect the small intestinal function and whether these changes would lead to obesity prevention in rats fed with high-fat diet. Three groups of weaned male rats (ad lib. fed; rats fed with diet containing 15% w/w of citrus pectin; restrictedly pair-fed rats) were fed with either a standard diet (9.5% fat) or a high-fat diet (30% fat) for 10 days. Results Our results revealed that pectin feeding led to significant decreases in body weight, energy intake and fat pad weight in rats fed with the standard as well as high-fat diet. Moreover, compared to the restrictedly pair-fed rats, in both groups of rats fed with the diet containing pectin, significant decrease in duodenal alkaline phosphatase (AP) activity was observed in histochemically stained cryostat sections. In contrast, despite their lower energy intake, restrictedly pair-fed rats showed similar fat pad deposition accompanied by unchanged values of AP activity in comparison to the controls. Conclusions Our findings indicate that daily pectin consumption could be beneficial in suppressing body weight gain and reducing probability of obesity risk in rats fed with a high-fat diet.

Cholecystokinin but not ghrelin stimulates mucosal bicarbonate secretion in rat duodenum: Independence of feeding status and cholinergic stimuli

Cholecystokinin (CCK) is an important regulator of food digestion but its influence on small intestinal secretion has received little attention. We characterized effects of CCK-8, ghrelin and some related peptides on duodenal HCO3− secretion in vivo and demonstrated CCK-induced calcium signaling in acutely isolated enterocytes.A segment of proximal duodenum with intact blood supply was cannulated in situ in anaesthetized rats. Mucosal HCO3− secretion was continuously recorded (pH-stat). Peptides were administrated to the duodenum by close intra-arterial infusion. Clusters of duodenal enterocytes were attached to the bottom of a perfusion chamber. The intracellular calcium concentration ([Ca2+]i) was examined by dual-wavelength imaging.CCK-8 (3.0, 15 and 60 pmol/kg,h) caused dose-dependent increases (p<0.01) in duodenal alkaline secretion in both overnight fasted and continuously fed animals. The CCK1R-antagonist devazepide but neither the CCK2R-antagonist YMM022 nor the melatonin MT2-selective antagonist luzindole inhibited the rise in secretion. Atropine decreased sensitivity to CCK-8. The appetite-related peptide ghrelin was without effect on the duodenal secretion in fasted as well as fed animals. Superfusion with CCK-8 (1.0-50 nM) induced [Ca2+]i signaling in acutely isolated duodenal enterocytes. After an initial peak response, [Ca2+]i returned to near basal values within 3–5min. Devazepide but not YMM022 inhibited this [Ca2+]i response.Low doses of CCK-8 stimulate duodenal alkaline secretion and induce enterocyte [Ca2+]i signaling by an action at CCK1 receptors. The results point to importance of CCK in the rapid postprandial rise in mucosa-protective duodenal secretion.

Development of selective non-peptide angiotensin II type 2 receptor agonsists

The development of the first drug-like selective angiotensin II type 2 (AT(2)) receptor agonist (22) derived from the non-selective angiotensin II type 1 (AT( 1)) receptor/AT(2) receptor agonist L-162,313 is presented. Compound 22 with a K(i) value of 0.4 nM for the AT( 2) receptor and a K(i) > 10 microM for the AT(1) receptor induces outgrowth of neurite cells, stimulates p42/p44( mapk), enhances in vivo duodenal alkaline secretion in Sprague-Dawley rats and lowers the mean arterial blood pressure in anaesthetised spontaneously hypertensive rats. Thus, the peptidomimetic 22 exerts a similar biological response as the endogenous peptide angiotensin II after selective activation of the AT(2) receptor. In addition, Compound 22 has a bioavailability of 20-30% after oral administration and a half-life estimated to four hours in the rat. Compound 22 will therefore serve as a valuable research tool enabling studies of the function of the AT(2) receptor in more detail.

Design, Synthesis, and Biological Evaluation of the First Selective Nonpeptide AT2 Receptor Agonist

The first druglike selective angiotensin II AT(2) receptor agonist (21) with a K(i) value of 0.4 nM for the AT(2) receptor and a K(i) > 10 microM for the AT(1) receptor is reported. Compound 21, with a bioavailability of 20-30% after oral administration and a half-life estimated to 4 h in rat, induces outgrowth of neurite cells, stimulates p42/p44(mapk), enhances in vivo duodenal alkaline secretion in Sprague-Dawley rats, and lowers the mean arterial blood pressure in anesthetized, spontaneously hypertensive rats. Thus, the peptidomimetic 21 exerts a similar biological response as the endogenous peptide angiotensin II after selective activation of the AT(2) receptor. Compound 21, derived from the prototype nonselective AT(1)/AT(2) receptor agonist L-162,313 will serve as a valuable research tool, enabling studies of the function of the AT(2) receptor in more detail.

Duodenal alkaline secretion: its mechanisms and role in mucosal protection against gastric acid

<h2>Abstract</h2> Duodenal mucosa, especially its proximal portion, is exposed to intermittent pulses of gastric acid (H⁺). This review summarises the mechanisms of duodenal bicarbonate (HCO₃⁻) secretion and their role in protecting duodenal epithelium against gastric H⁺. Duodenal epithelium is a leaky barrier against gastric H⁺, which diffuses into duodenocytes, but fails to damage them due to: (a) an enhanced expression of cyclooxygenase, producing protective prostaglandins and expression of nitric oxide synthase, releasing nitric oxide, both stimulating duodenal HCO₃⁻ secretion and (b) the release of several neurotransmitters also stimulating HCO₃⁻ secretion such as vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, acetylcholine and melatonin. At the apical duodenocyte membrane, several HCO₃⁻/Cl⁻ anion exchangers operate in response to luminal H⁺ to extrude HCO₃⁻ into duodenal lumen. In baso-lateral duodenocyte membrane, both non-electrogenic and electrogenic Na⁺–HCO₃⁻ cotransporters are activated after exposure of duodenum to gastric H⁺, causing inward movement of HCO₃⁻ from extracellular fluid to duodenocytes. There are also at least three Na⁺/H⁺ exchangers, eliminating H⁺ which diffused into these cells. The <i>Helicobacter pylori</i> infection with gastric metaplasia in the duodenum and <i>bacterium</i> inoculation results in the inhibition of HCO₃⁻ secretion by its endogenous inhibitor dimethyl arginine, resulting in ulcerogenesis.

Duodenal defence mechanisms: role of mucosal bicarbonate secretion

The duodenal epithelium secretes bicarbonate at higher rates than does the stomach (or more distal small intestine) and the duodenal secretion is currently accepted as the most important defence mechanism against acid discharged from the stomach. HCO3- entering the continuous layer of visco-elastic mucus gel on top of the epithelial surface maintains pH in its cell-facing portion at neutrality at acidities encountered in the healthy duodenum. The secretion is decreased in patients with acute and chronic duodenal ulcer disease and is inhibited by non-steroidal anti-inflammatory agents. Studies of the neurohumoral control of the duodenal alkaline secretion and of acid/base transport processes and intracellular signaling in duodenal enterocytes are currently of great research interest.

Gastrointestinal cytoprotection by prostaglandin E and EP receptor subtypes

Endogenous prostaglandins (PGs) play important roles in modulating the mucosal integrity and various functions of the gastrointestinal tract. Among them, E-type PGs are most effective in these actions. This article reviews recent studies dealing with the relationship of the cytoprotective action of PGE2- and EP-receptor subtypes in the gastrointestinal mucosa. PGE2 exerts gastric cytoprotection against HCl/ethanol and indomethacin. These effects were mimicked by only EP1 agonists and attenuated by EP1 antagonists. Likewise, the adaptive cytoprotection induced by a mild irritant was attenuated by EP1 antagonists as well as indomethacin. On the other hand, the protective effect of dmPGE2 against indomethacin-induced small intestinal lesions was mimicked by only EP3 and EP4 agonists. Similar results were obtained in EP-receptor knockout mice; i.e., PGE2 failed to exhibit both direct and adaptive cytoprotection in EP1-receptor knockout mice, while the protective action in both the duodenum and small intestine was hampered in EP3-receptor knockout mice. The underlying mechanism related to these actions of PGE2 in the stomach, duodenum or small intestine may be related to inhibition of stomach contraction, stimulation of duodenal alkaline secretion, or suppression of bacterial translocation due to inhibition of intestinal contraction as well as stimulation of mucus secretion, respectively.

Identification of transport abnormalities in duodenal mucosa and duodenal enterocytes from patients with cystic fibrosis

Background & Aims: The duodenum is a cystic fibrosis transmembrane conductance regulator (CFTR)-expressing epithelium with high bicarbonate secretory capacity. We aimed to define the role of CFTR in human duodenal epithelial bicarbonate secretion in normal (NL) subjects and patients with cystic fibrosis (CF). Methods: Endoscopic biopsy specimens of the duodenal bulb were obtained from 9 CF patients and 16 volunteers. Tissues were mounted in modified Ussing chambers. Bicarbonate secretion and short-circuit current (Isc) were quantitated under basal conditions and in response to dibutyryl adenosine 3',5'-cyclic monophosphate (db-cAMP), carbachol, and the heat-stable toxin of Escherichia coli (STa). Duodenocytes were also isolated and loaded with the pH-sensitive fluoroprobe BCECF/AM, and intracellular pH (pH i) was measured at rest and after intracellular acidification and alkalinization. Results: Basal HCO 3 − secretion and Isc were significantly lower in the CF vs. NL duodenal mucosa. In contrast to NL, db-cAMP failed to alter either HCO 3 − or Isc in CF tissues. However, in CF, carbachol resulted in an electroneutral HCO 3 − secretion, whereas STa induced electrogenic HCO 3 − secretion that was similar to NL. In CF and NL duodenocytes, basal pH i and recovery from an acid load were comparable, but pH i recovery after an alkaline load in CF duodenocytes was Cl − dependent, whereas in NL duodenocytes it was Cl − independent. Conclusions: These findings implicate CFTR in NL duodenal alkaline transport and its absence in CF. Although duodenal bicarbonate secretion is impaired in CF tissues, alternate pathway(s) likely exist that can be activated by carbachol and STa. GASTROENTEROLOGY 2000;118:1051-1060

Acid/Base Transporters in Human Duodenal Enterocytes

Background: Duodenal mucosal bicarbonate secretion serves as a key defensive factor against mucosal injury. The purpose of the present study was to isolate human proximal duodenal enterocytes and identify their inherent acid/base transporters that participate in duodenal alkaline secretion. Methods: Biopsy specimens were obtained from the duodenal bulb in 18 healthy volunteers. Individual duodenal epithelial cells were isolated by means of a combination of calcium chelation and collagenase. Intracellular pH (pHi) was measured by the pH-sensitive dye BCECF and dynamic fluorescence ratio imaging. Results: Cytologic and histologic examination confirmed that isolated cells were of epithelial origin. In HCO3

Human proximal duodenal alkaline secretion is mediated by Cl-/HCO3- exchange and HCO3- conductance.

The proximal duodenal epithelium secretes bicarbonate into an adherent mucus layer, thereby protecting the mucosa from injury by gastric acid and pepsin. While bicarbonate secretion is stimulated and inhibited by a number of agonists and antagonists, the apical anion transport pathways have not been addressed fully. The objective was to assess if apical Cl-/HCO3- exchange and Cl-:HCO3- conductance are involved in duodenal mucosal bicarbonate secretion (DMBS). In healthy volunteers, the proximal 4 cm of duodenum was isolated, perfused with either saline or 4,4'-diisothiocyano-2,2'-disulfonic acid (DIDS), and bicarbonate secretion and transepithelial potential difference (PD) were stimulated by either PGE2 or the phosphodiesterase inhibitor theophylline to increase cyclic AMP. Luminal DIDS abolished PGE2-stimulated DMBS, yet had no effect on the increase in PD and failed to significantly alter theophylline-induced DMBS and PD. Therefore, in human proximal duodenum, it appears that PGE2 and cAMP activate distinct HCO3- transport pathways likely involving a DIDS-sensitive Cl-/HCO3- exchanger and DIDS-insensitive HCO3- conductance.

Acid-induced increase in duodenal mucosal alkaline secretion in the rat involves the L-arginine/NO pathway.

Duodenal mucosal alkaline secretion increases in response to hydrochloric acid exposure. The tentative role of nitric oxide (NO) in the mediation of this response was investigated. The mucosal alkaline output by a duodenal segment was recorded by in situ titration in chloralose-anaesthetized rats. In some experiments the duodenal blood flow was estimated by laser-Doppler flowmetry. Exposure of the duodenum to acid (0.01 M HCl, 5 min) increased the alkaline secretion by approximately 85%. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 10 mg kg-1 intravenously or 0.3 mM intraluminally) blocked the secretory increment after mucosal acid exposure. Mean arterial pressure and basal alkaline secretion were markedly raised, whereas duodenal blood flow was decreased, when L-NAME was given intravenously (i.v.). Intraluminal (i.l.) administration left mean arterial pressure as well as duodenal blood flow unaltered, and the duodenal mucosal alkaline secretion was only slightly elevated. The stereoisomer NG-nitro-D-arginine methyl ester (D-NAME) had no effect on either basal or acid-induced duodenal alkaline output. In animals receiving L-arginine (10 mg kg-1 min-1 i.v., or 3 mM i.l.) and L-NAME, the acid exposure elicited an increase in duodenal mucosal alkaline secretion, similar to that observed in controls. The results suggest that the acid-induced increase in duodenal mucosal alkaline secretion involves NO synthesis, which takes place close to the lumen, probably within the mucosa.

CFTR mediates cAMP- and Ca2+-activated duodenal epithelial HCO3- secretion.

The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in duodenal alkaline secretion has not been directly examined. The aims of this series of experiments were to determine if CFTR mediates basal and stimulated duodenal epithelial HCO3- secretion. Utilizing the cystic fibrosis murine model (cftr(m1UNC)), we compared normal [CFTR(+/+)] littermates (34-46 days old) with CFTR(-/-) animals (34-39 days old). Anesthesia was induced and maintained with intraperitoneal Hypnorm-midazolam. The proximal duodenum (4-7 mm) was cannulated and perfused with 154 mM NaCl. Either forskolin (10(-6)-10(-4) M) or carbachol (10(-6)-10(-3) M) was perfused intraluminally to activate adenosine 3',5'-cyclic monophosphate (cAMP)- and Ca2+-mediated HCO3- secretion, respectively. Effluent volumes were weighed and HCO3- quantitated by back titration. Basal HCO3- secretion was diminished significantly (P < 0.01) in CFTR(-/-)vs. normal CFTR(+/+) mice (2.8 +/- 0.5 vs. 5.3 +/- 0.4 micromol x cm(-1) x h(-1)). Moreover, in CFTR(-/-) mice, both forskolin- and carbachol-stimulated peak HCO3- secretions were fourfold less compared with those in CFTR(+/+) littermates (3.7 +/- 0.2 vs. 15.6 +/- 2.1 and 4.7 +/- 0.3 vs. 14.2 +/- 2.5 micromol x cm(-1) x h(-1), respectively; P < 0.01). In conclusion, CFTR plays a significant role in mediating basal, cAMP-, and Ca2+-activated duodenal epithelial HCO3- secretion.

ACE inhibition by enalaprilate stimulates duodenal mucosal alkaline secretion via a bradykinin pathway in the rat.

The effects of enalaprilate on duodenal mucosal alkaline secretion (in situ titration) and mean arterial blood pressure were investigated in chloralose-anesthetized male rats. A bolus injection of enalaprilate (0.7 mg/kg intravenously) increased alkaline secretion by about 60%, and this response was resistant to guanethidine (5 mg/kg intravenously), splanchnicotomy, and vagotomy. Furthermore, angiotensin II infusion (0.25-2.5 microg/kg/hr intravenously) following the administration of enalaprilate failed to influence this response. Bradykinin (10(-6)-10(-4) M) applied topically to the serosal surface of the duodenal segment under study increased dose-dependently the duodenal mucosal alkaline secretion, an effect that could be blocked by the selective bradykinin receptor subtype-2 antagonist HOE140 (100 nmol/kg intravenously). HOE140 also antagonized the response to enalaprilate. These data suggest that enalaprilate increases duodenal mucosal alkaline secretion via a local bradykinin pathway involving receptors of the bradykinin receptor subtype-2 antagonist, rather than by blockade of endogenous angiotensin II or by central autonomic neural regulation.

Interaction between prostanoids, NO, and VIP in modulation of duodenal alkaline secretion and motility.

The relation between duodenal motility and duodenal mucosal alkaline secretion (DMAS) was examined in anesthetized rats. The duodenum was perfused with saline, and DMAS was determined by titration. Duodenal motility, assessed by intraluminal pressure measurements, was induced by indomethacin and/or N omega-nitro-L-arginine methyl ester (L-NAME) and inhibited by iloprost or vasoactive intestinal peptide (VIP). Six of 66 rats showed spontaneous duodenal contractions. Basal DMAS was higher in these rats than in those without contractions. Rats treated with indomethacin and L-NAME before abdominal operation exhibited duodenal motility postoperatively and had higher DMAS than in controls. Iloprost abolished both the duodenal motility increase and increase in DMAS induced by indomethacin. L-NAME-induced motility and increase in DMAS were antagonized by L-arginine. VIP increased DMAS without affecting motility. VIP abolished indomethacin-induced motility and augmented indomethacin-stimulated DMAS. VIP reduced L-NAME-induced motility and slightly increased L-NAME-stimulated DMAS. It is concluded that DMAS varies with duodenal motility. Prostaglandins and NO inhibit duodenal motility, thereby indirectly reducing DMAS. VIP may have dual effects on DMAS, an inhibitory action mediated via smooth muscle relaxation and a stimulatory action independent of motility.

Cyclic adenosine-3',5'-monophosphate production is greater in rabbit duodenal crypt than in villus cells.

Duodenal surface epithelial cells secrete bicarbonate. Agonists of duodenal alkaline secretion (such as vasoactive intestinal polypeptide (VIP), prostaglandin E2 (PGE(2)), and forskolin) increase intracellular cyclic adenosine-3', 5-monophosphate (cAMP), and cAMP stimulates Cl-HCO(3)- exchange in duodenal brush border membrane vesicles. As intestinal villus and crypt cells differ in function, our aims were to contrast cAMP generation in duodenal villus versus crypt cells in response to VIP, PGE(2), and forskolin. Villus and crypt rabbit duodenal enterocytes were isolated by calcium chelation. To prevent the degradation of cAMP in vitro, phosphodiesterase activity was inhibited. cAMP production was quantitated in response to VIP (10(-10)-10(-5)M), PGE(2) (10(-10)-10(-4)M), and forskolin (10(-8)-10(-3)M). In crypt cells cAMP generation was approximately 10-fold greater (P < 0.001) in response to VIP, PGE(2), and forskolin than to villus cells. The relative orders of potency (that is, D(50), VIP > PGE(2) > forskolin) and efficacy (that is, V max, forskolin > VIP and PGE(2)) were similar in villus and crypt cells. cAMP production is greater in duodenal crypt than in villus enterocytes at rest and in response to forskolin, VIP, and PGE(2), suggesting that alkaline secretion may differ along the villus-to-crypt axis.

Duodenal mucus and alkaline secretion in vivo; effects of cyclo-oxygenase inhibitor, nitric oxide synthase inhibitor and luminal acid

Duodenal mucus and alkaline secretion in vivo; effects of cyclo-oxygenase inhibitor, nitric oxide synthase inhibitor and luminal acid

Theophylline-stimulated human duodenal alkaline secretion is likely due to anion conductance: [formula omitted], M.A. Koss, V.S. Pratha, R.C. Rapier, D.L. Hogan and J.I. Isenberg. Division of Gastroenterology, Department of Medicine, University of California at San Diego, San Diego, CA

Theophylline-stimulated human duodenal alkaline secretion is likely due to anion conductance: [formula omitted], M.A. Koss, V.S. Pratha, R.C. Rapier, D.L. Hogan and J.I. Isenberg. Division of Gastroenterology, Department of Medicine, University of California at San Diego, San Diego, CA

Effects of nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester on duodenal alkaline secretory and ulcerogenic responses induced by mepirizole in rats

The inhibition of nitric oxide (NO) production by NO synthase inhibitors stimulates HCO3- secretion in the rat duodenal mucosa. Therefore, we examined the effects of NG-nitro-L-arginine methyl ester (L-NAME, the NO synthase inhibitor) and nitroprusside (the exogenous NO donor) on the duodenal HCO3- and ulcerogenic responses in anesthetized rats. Animals were administered mepirizole (200 mg/kg, subcutaneously) for induction of duodenal ulcers, and gastric acid and duodenal HCO3- secretions were measured with or without pretreatment with L-NAME (5 mg/kg, intravenously) or nitroprusside (4 mg/kg, intravenously). Mepirizole increased acid secretion, decreased the acid-induced duodenal HCO3- secretion, and induced hemorrhagic lesions in the proximal duodenum. The inhibition of NO production by L-NAME potentiated the acid secretory response, increased the duodenal HCO3- secretion, and prevented the duodenal lesions, and these changes were all antagonized by simultaneous administration of L-arginine (200 mg/kg, intravenously) but not D-arginine. On the other hand, nitroprusside slightly reduced the acid response but further decreased the HCO3- output, resulting in aggravation of duodenal lesions induced by mepirizole. These data suggest that the inhibition of endogenous NO production by the NO synthase inhibitor L-NAME increases duodenal HCO3- secretion and protects the duodenal mucosa against acid injury.

Role of dopamine and other stimuli of mucosal bicarbonate secretion in duodenal protection

Duodenal mucosal secretion of bicarbonate is one main mechanism in the protection of this epithelium against luminal acid. The duodenal secretagogue vasoactive intestinal polypeptide, at doses not affecting mucosal blood flow, protects against acid-induced morphological changes. Some sigma receptor ligands, which increase the duodenal alkaline secretion, prevent duodenal but not gastric mucosal ulceration. Dopamine D-1 receptor agonists and the peripherally acting catechol-O-methyl-transferase (COMT) inhibitor nitecapone stimulate the bicarbonate secretion in the rat and a similar increase in secretion has been observed in human volunteers. COMT inhibitors decrease tissue degradation of catecholamines, including dopamine. The D-2 agonist bromocriptine, in contrast, decreases the secretion. These results, indicating that the bicarbonate secretion is stimulated via peripheral dopamine D-1 receptors, are supported by the finding that dopamine D-1 (but not D-2) agonists increase the production of cyclic AMP in isolated duodenal enterocytes. The increase in mucosal alkaline secretion may contribute to the previously observed ulceroprotective actions of dopaminergic compounds.