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Biomedical subjects

D L Hogan

Publications and source records attributed to D L Hogan.

At least 37 records · Page 2Linked to original sources
PubMed1993

Cigarette smoking inhibits acid-stimulated duodenal mucosal bicarbonate secretion.

OBJECTIVE: To determine the effect of cigarette smoking on proximal duodenal mucosal bicarbonate secretion, an important defense mechanism against acid and peptic damage. DESIGN: Prospective study. SETTING: Clinical research laboratory in a university hospital. PATIENTS: Thirteen healthy adults (7 smokers and 6 nonsmokers) who had no history of peptic ulcer disease. INTERVENTIONS: Participants smoked (1 cigarette/15 min during a period of 1 hour, smokers only) or sham smoked (puffing on an unlit cigarette) during duodenal perfusion with either saline, hydrochloric acid, or prostaglandin E2 (PGE2). MEASUREMENTS: Collection of proximal duodenal secretions using a modified duodenal tube with occluding balloons and quantitation of duodenal mucosal bicarbonate secretion. RESULTS: During sham smoking both smokers and nonsmokers had comparable basal as well as H(+)-stimulated and PGE2-stimulated duodenal mucosal bicarbonate secretion. Compared with sham smoking, smoking did not significantly alter basal bicarbonate secretion (201 mumol/cm per hour [95% CI, 152 to 250 mumol/cm per hour] compared with 178 mumol/cm per hour [CI, 134 to 222 mumol/cm per hour], respectively). However, compared with sham smoking, smoking markedly reduced (P < 0.01) the increase in duodenal bicarbonate secretion in response to luminal acidification by approximately 80% (from 242 mumol/cm per hour [CI, 41 to 443 mumol/cm per hour] to 53 mumol/cm per hour [CI, -107 to 197 mumol/cm per hour]); a decrease was observed in each participant. In contrast, smoking had no significant effect on the response to luminal PGE2. CONCLUSIONS: Cigarette smoking markedly inhibited acid-stimulated human duodenal mucosal bicarbonate secretion. This adverse effect of smoking may, at least in part, explain the role of cigarette smoking in the pathogenesis and natural history of duodenal ulcer disease.

Adult↗
PubMed1993

The enteric nervous system modulates mammalian duodenal mucosal bicarbonate secretion.

BACKGROUND: Interaction of the enteric nerves in regulating mammalian duodenal mucosal bicarbonate secretion is not well understood. The purpose of the present experiments was to evaluate the role of the enteric nervous system on bicarbonate secretion from rabbit duodenal mucosa in vitro. METHODS: Proximal duodenum from male New Zealand White rabbits was stripped of seromuscular layers, mounted in Ussing chambers, and studied under short-circuited conditions. Effects of electrical field stimulation, vasoactive intestinal polypeptide (VIP), carbachol, prostaglandin E2 (PGE2), dibutyryl-cyclic adenosine monophosphate (db-cAMP), and the neurotoxin tetrodotoxin (TTX) and muscarinic blockade by atropine were studied. RESULTS: Electrical field stimulation significantly (P < 0.01) stimulated bicarbonate secretion, short-circuit current (Isc), and electrical potential difference (PD) that was sensitive to both TTX and atropine. VIP-stimulated bicarbonate secretion was significantly inhibited by TTX (-73%), yet Isc and PD remained unchanged. Atropine decreased VIP-induced bicarbonate secretion (-69%) and Isc (-43%). Carbachol-stimulated bicarbonate secretion, Isc, and PD were abolished by atropine, whereas TTX was without affect. Neither TTX nor atropine had a significant effect on PGE2 or db-cAMP-stimulated bicarbonate secretion. CONCLUSIONS: These results suggest that (1) enteric nerve stimulation activates an acetylcholine receptor that in turn stimulates duodenal epithelial bicarbonate secretion; (2) VIP stimulates bicarbonate secretion, in large part, via the enteric nervous system; and (3) PGE2 and cAMP stimulate bicarbonate secretion independent of the enteric nervous system.

Animals↗
PubMed1993

Bicarbonate transport by rabbit duodenum in vitro: effect of vasoactive intestinal polypeptide, prostaglandin E2, and cyclic adenosine monophosphate.

BACKGROUND: Duodenal surface cells secrete bicarbonate that provides a barrier against injury. The current experiments were performed to identify duodenal bicarbonate regulatory and transport pathways. METHODS: Rabbit proximal duodenal mucosa were mounted in chambers under short-circuited conditions. Bicarbonate transport, short-circuit current (Isc), and potential difference (PD) were quantitated in response to prostaglandin E2 (PGE2), vasoactive intestinal polypeptide (VIP), and dibutyryl cyclic adenosine monophosphate (db-cAMP). Anoxia (N2), 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and Cl(-)-free solutions, ouabain, and Na-free solutions were also studied, as was the effect of VIP and PGE2 on duodenocyte cAMP. RESULTS: PGE2, VIP, db-cAMP, and theophylline significantly increased bicarbonate secretion, Isc, and PD. Ouabain, Na(+)-free bathing solutions, and anoxia (N2) inhibited the responses. DIDS and Cl(-)-free solutions abolished the PGE2-induced response, reduced the response to VIP by about 50%, and had no effect on the response to db-cAMP. After PGE2 and VIP, cAMP concentration increased, yet was likely independent of bicarbonate secretion. CONCLUSIONS: Mammalian duodenal HCO3- transport requires Na+, Na+/K(+)-adenosine triphosphatase and O2-dependent metabolic pathways and is stimulated by PGE2, VIP, and cAMP, acting by distinct pathways.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1993

The effect of acute emotional stress on gastric acid secretion in normal subjects and duodenal ulcer patients.

Emotional stress (ES) has been proposed as a possible factor in the pathogenesis of duodenal ulcer (DU) disease. Modern, well-controlled studies on the effect of ES on gastric acid secretion (GAS) in both normal healthy subjects and patients with inactive DU are lacking. Ten normal (N) men and 10 men with inactive DU were observed on 2 separate days. In random order, subjects either underwent dichotomous listening (DL) to induce stress or a control (non-DL) test. In addition to measuring GAS in 15-min periods, heart rate and blood pressure were measured every 7.5 min, and visual analog scale measures of emotion (relaxation, anxiety, anger, tension, and depression) were monitored. Subjects underwent 2 separate study days, 1 h of a basal period followed by 1 h of a DL session or 1 h of a basal period followed by 1 h of a non-DL control session; the order of the days was randomized. In both N and DU emotional stress by DL induced these parameters significantly: increased heart rate; raised systolic and diastolic blood pressures (p < 0.01); increased anxiety, anger, and tension (p < 0.03); and decreased relaxation (p < 0.01). The non-DL control test did not alter cardiovascular or emotion measures in either group. While ES did not alter GAS in N subjects, ES increased GAS when compared to the basal state (p < 0.02) and when compared to the control test (p = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Anti-secretory effects and pharmacokinetics of low dose ranitidine.

The purpose of this study was to examine the anti-secretory effect of low doses of orally administered ranitidine on meal-stimulated gastric acid secretion and assess its pharmacokinetics. The effect of 20, 40, 60 and 80 mg of ranitidine p.o. and placebo were tested on 5 separate days (Latin square, double-blind) in 15 healthy males (mean age 35 years). Gastric acid secretion was measured prior to and for 8 h following two sequential mixed liquid meals administered at 4-h intervals. Venous blood samples were obtained at frequent intervals before and following each dose for determination of plasma ranitidine concentration by high pressure liquid chromatography. Each dose of ranitidine significantly (P < 0.01) decreased the peak and cumulative 4-h acid secretory responses to the first meal (range 58-93%), and the 60 and 80 mg doses significantly inhibited the response to the second meal by 31 and 43%, respectively. Total 8-h meal-stimulated acid outputs were decreased significantly in a dose-related manner (range 38-73%). Peak plasma ranitidine occurred approximately 1 h after dosing. Ranitidine tmax, t1/2 and clearances were independent of dose; however, AUC and Cmax were dose-related. Inhibition of acid secretion was related to plasma ranitidine concentration; the mean IC50 was 27 (+/- 6.4) ng/ml. We conclude that modest doses (equivalent to 7-27% of the daily therapeutic dose) of ranitidine effectively suppress meal-stimulated gastric acid secretion in a dose-related manner. If these doses are of clinical efficacy, it may be possible for substantial cost savings to occur.

Administration, Oral↗
PubMed1993

Gastric acid suppression is greater during intravenous ranitidine infusion versus bolus injections of famotidine.

It has been proposed that famotidine may be effective in maintaining intragastric pH > or = 4 for up to 12 h with a single i.v. 20 mg bolus injection and thereby prevent acute stress-related mucosal haemorrhage. The present study was designed to compare a ranitidine continuous i.v. infusion (6.25 mg/h) vs. famotidine bolus injection (20 mg every 12 h) on 24-h intragastric pH and gastric acid secretion. Twenty-eight healthy volunteers (15 males, 13 females; 20-56 years) participated in two 24-h treatment periods; each test was in random order separated by 7-10 days. After an overnight fast, subjects were intubated and gastric pH and acid secretion measured hourly. Whereas ranitidine maintained gastric pH above 4 for the entire 24-h period, mean pH steadily decreased to a nadir of 2.9 and 3.7, respectively, 12 h after each famotidine injection (P < 0.01 vs. ranitidine). Furthermore, gastric acid secretion increased to 4.4 +/- 1.2 mmol/h 12 h after famotidine injection compared to 1.1 +/- 0.3 mmol/h with ranitidine (P < 0.01). We conclude that ranitidine delivered as a continuous i.v. infusion (6.25 mg/h) is superior to bolus famotidine injections (20 mg) at 12-h intervals in suppressing gastric acid secretion and maintaining an intragastric pH > or = 4. More frequent famotidine dosing, or delivery by continuous i.v. infusion, may be required to provide prolonged acid suppression.

Adult↗
PubMed1993

Age-related differences in the pharmacokinetics and pharmacodynamics of lansoprazole.

1. The pharmacokinetics and pharmacodynamics of lansoprazole, an antisecretory and antiulcer agent, were evaluated in 12 older (> 60 years) and 12 younger (< 60 years) healthy men. 2. Doses of lansoprazole (15 or 30 mg) or placebo were each given once daily for 7 consecutive days in this randomized, double-blind, three-way crossover study. Plasma concentrations and urinary excretion of lansoprazole and its metabolites, and gastric acid secretion were monitored after dosing on days 1 and 7 of each treatment period. 3. Within each age group, lansoprazole pharmacokinetics were linear. The mean clearance and elimination half-life of lansoprazole were about 40% lower and higher, respectively, in the older subjects (CL0: 12-14 vs 20-24 1 h(-1); t1/2,z: 1.90-2.19 vs 1.26-1.44 h). 4. At each dose level, acid secretion was more inhibited in the older group. However, the AUC associated with a 50% decrease in acid secretion was similar (849 vs 892 ng ml(-1) h) for both age groups. Multiple dosing decreased the maximum possible inhibition more in the older group than in the younger group. 5. Since the decrease in acid output associated with equivalent AUCs on day 1 was similar for the two age groups, the greater difference between day 1 and day 7 secretion in the older group indicates that recovery of secretory activity may decline with increasing age.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1992

Theophylline and prostaglandin E2 on duodenal bicarbonate secretion: role for 5'-cyclic adenosine monophosphate.

Cyclic adenosine monophosphate (cAMP) has been implicated as an intracellular "second" messenger in duodenal mucosal bicarbonate secretion in animals. The purpose of this study was to determine whether cAMP may mediate duodenal mucosal bicarbonate secretion in humans. In healthy volunteers, a 4-cm segment of proximal duodenum was isolated from gastric and pancreaticobiliary secretions. Either the phosphodiesterase inhibitor theophylline, prostaglandin (PG) E2, or a combination thereof was administered topically to the isolated duodenal mucosa. Theophylline (10(-2) mol/L) and PGE2 (10(-5)-10(-4) mol/L) each significantly increased bicarbonate secretion and transmucosal potential difference. Moreover, when theophylline and PGE2 were administered in combination, the duodenal bicarbonate output was additive compared to either agent alone. When theophylline was infused with increasing doses of PGE2, the dose-response curve was shifted to the left. Furthermore, increases in bicarbonate secretion and transmucosal potential difference were correlated significantly. These results suggest that cAMP may act as an intracellular mediator of human duodenal mucosal bicarbonate secretion.

Adult↗
PubMed1992

Measurement of gastric bicarbonate secretion in the human stomach: different methods produce discordant results.

Human gastric bicarbonate secretion has been measured by back-titration, from pH and pressure of carbon dioxide (PCO2) determinations (using the Henderson-Hasselbalch formula), and from equations based on gastric juice osmolality and [H+] (osmolality-[H+] method). Since these methods show large quantitative differences in their estimations of gastric bicarbonate secretion, we examined each to define the reasons for these discrepancies and establish guidelines for future work in this area. Bicarbonate recovery from 'non-parietal' secretions (0 to 80 mM HCO3) reacting with 'pure parietal secretion' (160 mM HCl) was studied both in vitro and in the pylorus-occluded healthy human stomach during acid suppression, exogenous acidification, and pentagastrin stimulation. The pH/PCO2 method estimated HCO3- accurately under anaerobic conditions in vitro, whereas the osmolality-[H+] method (with correction factors for osmolality incorporated by us) was accurate under aerobic conditions. In the acid-suppressed stomach back-titration was significantly more accurate than the pH/PCO2 method. In the exogenously acidified and pentagastrin-stimulated stomachs the pH/PCO2 method underestimated bicarbonates, and the osmolality-[H+] method was spuriously elevated in the low range and diminished at high bicarbonate concentrations. Estimates of 'basal' bicarbonate secretion (at zero added bicarbonate) were severalfold higher by the osmolality-[H+] method (5.26 +/- 0.33 mmol/h) than by the pH/PCO2 method (1.20 +/- 0.23 mmol/h) or back-titration (0.65 +/- 0.14 mmol/h). In conclusion, gastric bicarbonate was determined most correctly by back-titration in the acid-suppressed stomach, whereas measurement of bicarbonate in the acid-secreting stomach was not accurate with any method.

Adult↗
PubMed1992

pH threshold for human duodenal bicarbonate secretion and diffusion of CO2.

Gastric acid enters the proximal duodenum both as free and buffered H+. The procedures in this study were threefold: (a) to determine the pH threshold for duodenal mucosal bicarbonate secretion, iso-osmolar citric acid (pH 2.5-4.0; H+, 1.1 mmol) was infused; (b) to examine the effect of varying acid loads (H+, 0.4-5.1 mmol), citric acid (pH 3.0) was perfused; and (c) to quantitate duodenal diffusion of CO2, citric acid (pH 5.0) gassed with CO2 (PCO2, 0-210 mm Hg) was tested. Basal bicarbonate secretion was similar on each test day, 230 mumol/cm.h. Citric acid at pH 2.5 and 3.0 increased bicarbonate output equally to about 560 mumol/cm.h (similar to 2 mmol of 100 mmol/L HCl); citric acid at pH 3.5 and 4.0 had no effect. Varying the acid load increased bicarbonate output similarly. Duodenal loss of CO2 was minimal (4%) with infusion of 50 mm Hg PCO2 and increased to approximately 25% (15 mm Hg/min) at higher PCO2 values. It is concluded that (a) the pH threshold for human duodenal mucosal bicarbonate secretion is 3.0; (b) a pH-sensitive, rather than an acid load-sensitive, regulatory process exists; and (c) CO2 loss plateaus at 15 mm Hg/min at a PCO2 of 200 mm Hg.

Adult↗
PubMed1991

Cholinergic regulation of human proximal duodenal mucosal bicarbonate secretion.

Cephalic-vagal stimulation affects a number of upper gastrointestinal secretory and motility events. The purpose of this study was to examine the role of vagal-cholinergic regulation on human proximal duodenal mucosal HCO-3 secretion. The duodenal bulb was isolated between balloons and perfused with 154 mM NaCl, and HCO-3 secretion was measured. Although cholinergic stimulation with bethanechol (50 micrograms.kg-1.h-1 iv) produced systemic effects, resting HCO-3 secretion was unchanged. Cephalic-vagal stimulation, induced by sham feeding, significantly increased duodenal HCO-3 secretion from a basal of 177 +/- 17 to 240 +/- 19 mumols.cm-1.h-1 (P less than 0.02). The response to sham feeding was approximately 50% of the peak response to acid-stimulated HCO-3 output. Atropine (22 micrograms/kg iv) inhibited basal HCO-3 secretion significantly (79 +/- 5%). However, the net incremental increases in duodenal mucosal HCO-3 secretion in response to luminal acidification and vagal stimulation were unaltered by atropine pretreatment. Additionally, indomethacin (100 mg po) failed to modify the response to vagal-stimulated HCO-3 secretion. These findings indicate that basal human proximal duodenal mucosal HCO-3 secretion is maintained largely by resting cholinergic innervation and is stimulated by cephalic-vagal stimulation. Furthermore, since the incremental HCO-3 responses to cephalic-vagal stimulation and luminal acidification were unaltered by atropine pretreatment, each is likely mediated by noncholinergic mechanisms.

Adult↗
PubMed1991

Effect of basal gastric acid secretion on the pharmacodynamics of ranitidine.

Twelve patients with inactive ulcer disease were administered placebo and ranitidine via bolus and continuous intravenous infusions, at doses ranging from 50 every 8 h, to 12.5 mg/h for 24 h. Gastric acid was collected for 20 min each h for 24 h, and ranitidine serum concentrations were measured approximately every 2 h, during each of the six study periods. Cosinor analysis of gastric acid secretion during placebo treatment revealed a significant circadian rhythm in all subjects. Mesor acid output ranged from 1.7 to 11.6 mmol/h (mean 5.6 +/- 2.8 mmol/h) and the amplitude ranged from 0.7 to 6.5 mmol/h (mean 2.8 +/- 1.6 mmol/h). Peak acid output (acrophase) occurred at 10 p.m. +/- 3 h. A pharmacodynamic model, relating ranitidine serum concentration to hourly acid secretion, was derived, which incorporated the circadian change in basal acid output. Data for this fractional response model included basal acid secretion--as determined by time of day, measured acid secretion, and associated serum ranitidine concentration. The 50% inhibitory concentration (IC50) for ranitidine ranged from 10-75 ng/ml, with a mean of 44 ng/ml. The variation in IC50 and in basal acid secretion combined to produce a wide variation in the pharmacodynamic response to ranitidine. The model-predicted serum concentrations, required to maintain acid secretion at 0.1 mmol/h, ranged from 250 to 1550 ng/ml, at the time of peak evening acid secretion. Despite a constant degree of acid inhibition by ranitidine during the day, higher serum concentrations are required during times of peak acid output to maintain adequate suppression of hydrogen ion secretion.

Adult↗
PubMed1990

Bolus or intravenous infusion of ranitidine: effects on gastric pH and acid secretion. A comparison of relative efficacy and cost.

STUDY OBJECTIVE: To compare the effects of intravenous bolus injection of ranitidine, continuous intravenous infusion of ranitidine, and placebo on gastric pH, acid secretion, and plasma ranitidine concentration during a 24-hour period, and to determine by survey the use, delivery methods, and costs of histamine H2-receptor antagonists in intensive care units. DESIGN: Double-blind, Latin-square randomized, prospective measurement of the gastric pH, acid output, and plasma ranitidine concentration over 24 hours in response to six treatment regimens in 12 patients with inactive duodenal ulcer. Eight regional hospitals were surveyed to obtain information on the use of histamine H2-receptor antagonists. INTERVENTIONS: Gastric acid secretion, pH, and plasma ranitidine were monitored for 24 hours on six separate days in response to placebo, intravenous bolus injection of ranitidine (50 mg every 8 hours and 75 mg every 12 hours), and continuous intravenous infusion of ranitidine (75, 150, and 300 mg every 24 hours). MEASUREMENTS AND MAIN RESULTS: Intravenous infusions were significantly more effective than bolus injections. After bolus injections, hourly gastric pH values fluctuated widely, from 7.6 to 1.6, whereas during continuous infusion of 150 mg and 300 mg, hourly pH values were 3.8 or greater. The gastric pH was greater than 4.0 in 75% +/- 5% and 83% +/- 6% of determinations done during continuous intravenous infusion of 150 mg and 300 mg, respectively. Fluctuations in the plasma ranitidine concentration corresponded with changes in gastric pH and acid secretion. Histamine H2-receptor antagonists were prescribed for about 75% of patients in intensive care units and were most commonly administered by bolus rather than infusion (5:1); the cost was approximately +40 per day less by infusion. CONCLUSIONS: On the basis of both efficacy and cost, intermittent bolus injections should be discontinued and replaced by continuous intravenous infusion in hospitalized patients requiring treatment with histamine H2-receptor antagonists. If ranitidine is used, either 150 mg or 300 mg administered as a 24-hour continuous infusion is most effective.

Adult↗
PubMed1990

Human duodenal mucosal bicarbonate secretion. Evidence suggesting active transport under basal and stimulated conditions.

When the proximal duodenum of animals or humans is perfused with isoosmolar NaCl, bicarbonate enters the luminal effluent. In addition, duodenal bicarbonate output is stimulated by luminal acidification and prostaglandins of the E class. The hypothesis that in vivo human duodenal bicarbonate transport persists in the absence of a plasma-to-lumen bicarbonate gradient and therefore is probably an active transport process was tested. In healthy subjects, a 4-cm segment of the proximal duodenum was isolated from gastric and pancreaticobillary secretions. Net duodenal bicarbonate secretion remained similar to basal levels during luminal perfusion with either 24 or 32 mM bicarbonate (each isoosmolar with plasma by the addition of NaCl). In addition, peak increases in acid-induced bicarbonate outputs with luminal perfusion of 154 mM NaCl and 32 mM NaHCO3 (+122 mM NaCl) were similar. Moreover, prostaglandin E2-stimulated bicarbonate secretion with perfusion of 154 mM NaCl and 32 mM NaHCO3 (+122 mM NaCl) was similar. It was concluded that in humans, proximal duodenal mucosal bicarbonate transport remains unaltered in the absence of a plasma-to-lumen bicarbonate gradient at rest and after stimulation with HCl or prostaglandin E2. These observations suggest that human proximal duodenal bicarbonate secretion involves active transport.

Adult↗
PubMed1990

Proximal duodenal prostaglandin E2 release and mucosal bicarbonate secretion are altered in patients with duodenal ulcer.

Proximal duodenal mucosal bicarbonate production is impaired in patients with duodenal ulcer disease. Because prostaglandins of the E class increase human proximal duodenal bicarbonate secretion, this study tested the hypothesis that endogenous prostaglandin E2 production is defective in patients with duodenal ulcer. Ten patients, five with active and five with inactive duodenal ulcer disease, were studied along with 10 normal volunteers. The proximal 4 cm of duodenum, the bulb, was isolated and continuously perfused with 154 mmol/L NaCl. Basal bicarbonate secretion was measured for 30 minutes. The test segment was then acidified with a physiological amount of HCl (2 mmol over 5 minutes), and acid-stimulated bicarbonate secretion was measured by pH/PCO2 and back-titration for 55 more minutes. Prostaglandin E2 was measured in the effluents by a radioimmunologic assay validated by gas chromatography-mass spectrometry. Compared with the normal subjects after luminal acidification, the duodenal ulcer patients had significantly greater PGE2 release and decreased total 1-hour bicarbonate output. The peak 5-minute acid-stimulated bicarbonate responses were not significantly different between the duodenal ulcer patients and normal subjects. After luminal acidification, PGE2 output remained elevated in the duodenal ulcer patients but returned promptly to basal in the normal subjects. Furthermore, the ratio of bicarbonate secreted to the amount of PGE2 released was significantly less in the ulcer patients. These findings suggest that patients with duodenal ulcer disease have an impaired mucosal bicarbonate response to endogenous PGE2. The increased acid-stimulated PGE2 response in duodenal ulcer patients suggests a compensatory phenomenon in response to the diminished mucosal bicarbonate production.

Bicarbonates↗
PubMed1990

Human duodenal mucosal bicarbonate secretion--physiological and clinical aspects.

Over the past few years, we have addressed some of the components that regulate human duodenal bicarbonate secretion (DBS) using a technique for the isolation of a 4-cm duodenal segment from gastric, pancreaticobiliary and distal intestinal secretions. Our observations are summarized as follows. Resting DBS is, to a large extent, maintained by vagal innervation; atropine decreases basal bicarbonate secretion by approximately 80%. Luminal acidification with HCI (H+) is a major physiological stimulus of DBS, resulting in a prompt and significant increase of 3- to 4-fold. H(+)-stimulated DBS is likely to be mediated, at least in part, by prostaglandins of the E class, and by VIP. Each of the latter stimulates DBS independently in a dose-related manner. Since atropine is without effect on the response induced by luminal H+ and sham feeding, in both cases DBS is probably stimulated via a non-cholinergic pathway(s). Moreover, since basal, H(+)- and PGE2-stimulated proximal DBS are unaltered when the plasma-to-lumen bicarbonate concentration gradient is abolished, it may be concluded that DBS in humans involves active transport processes. It is significant that compared to normal subjects, patients with duodenal ulcers show markedly diminished basal and H(+)-stimulated proximal DBS. Furthermore, there is surprisingly little overlap between duodenal ulcer (DU) patients and normal subjects. These findings suggest that an intrinsic cellular or subcellular defect in proximal duodenal mucosal bicarbonate secretion is present in patients with duodenal ulcer disease.

Acid-Base Equilibrium↗