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Background & Aims: Alcohol consumption may increase gastroesophageal reflux symptoms, cause damage to the esophageal mucosa, and/or promote carcinogenesis. However, reports about the association between alcohol and reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma are conflicting., Methods: Information relating to alcohol consumption, at age 21 and 5 years before the interview date, was collected from 230 reflux esophagitis, 224 Barrett's esophagus, and 227 esophageal adenocarcinoma patients and 260 frequency-matched population controls. Logistic regression analyses were used to compare alcohol consumption in the 3 case groups to controls with adjustment for potential confounders., Results: Population controls reporting gastroesophageal reflux symptoms were less likely than controls without symptoms to drink alcohol 5 years before the interview date (odds ratio [OR], 0.44, 0.20-0.99). No associations were observed between total alcohol consumption 5 years before the interview date and reflux esophagitis, Barrett's esophagus, or esophageal adenocarcinoma (OR, 1.26, 0.78-2.05; OR, 0.72, 0.43-1.21; and OR, 0.75, 0.46-1.22, respectively). Wine was inversely associated with reflux esophagitis (OR, 0.45, 0.27-0.75). Total alcohol consumption at age 21 years was significantly associated with reflux esophagitis (OR, 2.24, 1.35-3.74) but not with Barrett's esophagus or esophageal adenocarcinoma (OR, 1.06, 0.63-1.79 and OR, 1.27, 0.77-2.10, respectively)., Conclusions: Alcohol consumption in early adulthood may lead to the development of reflux esophagitis. More recent alcohol consumption does not appear to confer any increased risk of reflux esophagitis, Barrett's esophagus, or esophageal adenocarcinoma. In fact, wine consumption may reduce the risk of these 3 esophageal disorders.

Background & Aims: Acid has been shown to stimulate calcitonin gene-related peptide (CGRP) release from peripheral sensory afferent nerve endings in the stomach. The aim of this study was to determine whether endogenous CGRP was involved, by a neurocrine mechanism, in acid-mediated stimulation of somatostatin and inhibition of gastrin release., Methods: A two-compartment sleeve of antral mucosal/submucosal tissue was perfused to determine sensory nerve and endocrine cell responses to luminal acid. CGRP receptor antagonist, CGRP8-37, was used to inhibit the actions of endogenously released CGRP., Results: Perfusion of the antral sleeve lumen with media of increasing hydrogen ion concentration caused pH-dependent increases in CGRP and somatostatin release and decrease in gastrin release. CGRP8-37 inhibited significantly basal somatostatin (-36%) and stimulated basal gastrin (+65%) release (P < 0.02). Furthermore, CGRP8-37 administration prevented luminal acid-mediated inhibition of gastrin release and stimulation of somatostatin release. These results indicate that CGRP8-37 prevented acid-mediated feedback inhibition of gastrin release and acid-induced feedforward somatostatin release., Conclusion: These results suggest that CGRP plays an important role in the response of antral D and G cells to luminal acid and that local effector action of endogenous CGRP participates in regulation of antral regulatory peptide secretion.

Codons of noncoding DNA strands for peptides have been found to code for amino acids with hydropathic properties opposite to those of the native peptides. Synthetic peptides, designated as complementary peptides, with amino acid sequences coded by noncoding DNA strands of several peptide hormones have been shown to bind the native peptides. In some instances, antibodies to these complementary peptides have shown agonist or antagonist properties of the native hormones. In this study a peptide was synthesized based on codons complementary to messenger RNA for the carboxyl-terminal gastrin tetrapeptide. This complementary peptide bound radiolabeled human gastrin (G17). Antibodies to the complementary peptide competitively inhibited the binding of 125I-gastrin by canine fundic mucosal membrane preparations. These antibodies also showed gastrin agonist properties in that they stimulated canine gastric mucosal parietal cell [14C]aminopyrine uptake, used as an index of stimulation of gastric acid secretion. Competitive inhibition of 125I-gastrin binding by membrane receptors for gastrin and stimulation of [14C]-aminopyrine uptake by antibodies to the complementary peptide for the gastrin tetrapeptide are consistent with their recognition, binding, and occupancy of gastrin receptors.

Human gastrin I heptadecapeptide was administered by constant intravenous infusion to 7 adult male volunteers without gastrointestinal disease, and serum gastrin concentrations and responses of the lower esophageal sphincter (LES) pressure and gastric acid output were measured and compared. Significant responses in LES pressure were found at gastrin infusion rates which produced submaximal gastric acid output. These LES pressure responses were quantitatively smaller than those occurring concomitantly with similar total immunoreactive gastrin levels evoked by administration of a protein meal in the same subjects. These observations suggest that, although increases in serum gastrin concentrations may contribute to increases in LES pressure seen under physiological conditions after feeding, the increase in LES pressure produced by feeding cannot be explained exclusively on the basis of endogenous gastrin release.

This study was designed to examine and compare the nature of gastrinlike and cholecystokininlike peptides released into the portal and peripheral venous circulation in response to a peptone meal. Six dogs were prepared with portal venous catheters and gastric fistulas. Portal and peripheral venous sera were obtained before and after gastric infusion of a 10% peptone meal. Serum levels of gastrin and cholecystokinin immunoreactive peptides were determined by radioimmunoassay using two distinct peptide region-specific antibody preparations. These separate antibody preparations demonstrated specificity for (a) C-terminal tetradecapeptide gastrin (4-17hG17), heptadecapeptide gastrin (G17), and big gastrin (G34) (gastrin antibody); and (b) all biologically active forms of gastrin and cholecystokinin (gastrin-cholecystokinin antibody). Using the antibody preparation with specificity for gastrin and not cholecystokinin, the mean basal immunoreactive gastrin from portal (8.33 +/- 2.4 fmol/ml, mean +/- SEM) and from peripheral (6.19 +/- 0.9 fmol/ml) venous sera both increased after peptone infusion, with an early peak (2 min in portal and 4 min in peripheral serum) and a second peak at 30 min in both circulations. Measurements using antibodies with specificity for both cholecystokinin and gastrin yielded strikingly different results. The portal venous serum peptide concentration (49 +/- 10 fmol/ml) increased sharply within 30 s after peptone infusion to a single peak at 2 min (139 +/- 37 fmol/ml). The basal peripheral venous serum peptide concentration (43 +/- 8.8 fmol/ml) increased more gradually to a single peak at 8 min (78 +/- 14 fmol/ml). Studies with Sephadex (G-50 superfine) gel chromatography indicated that gastrin released in response to the peptone meal was primarily G17. However, of the peptides released in response to the peptone meal that were recognized by the gastrin-cholecystokinin antibody, greater than 80% were shown to be distinct from gastrin. Gel chromatographic studies demonstrated that peptone meal-stimulated immunoreactive cholecystokinin release consisted of two major peaks, eluting in positions identical to those of intact cholecystokinin (CCK33) and the octapeptide of cholecystokinin (CCK8).

The purpose of this study was to examine and quantify hepatic uptake and degradation of gastrin and cholecystokinin peptides. Rat livers were perfused in situ, without recirculation, with Krebs-Ringer bicarbonate (pH 7.4) containing 10% bovine erythrocytes, gassed with 95% O2-5% CO2. Gastrin and cholecystokinin peptide fragments of various lengths were injected into a portal vein via a sidearm syringe for over 1 min, and hepatic venous effluent was collected every minute for 20 min. After injection of 125I-labeled gastrin peptides more than eight amino acids in length, greater than 95% radioactivity appeared in the hepatic venous effluent, all of which was intact peptide, as determined by immunoprecipitation, trichloroacetic acid precipitation, and Sephadex gel chromatography. Decreasing the chain length to eight or less amino acids resulted in progressive increases in hepatic uptake and degradation of gastrin fragments. Injected cholecystokinin peptides greater than seven amino acids in length traversed the liver intact, whereas smaller cholecystokinin peptides were cleared by the liver. The liver eliminated greater than 90% of the biologically active carboxyl-terminal tetrapeptide amide common to gastrin and cholecystokinin. The results of this study indicate that gastrin and cholecystokinin peptides longer than seven amino acids traverse the liver without significant degradation, however, smaller peptides are progressively cleared during hepatic transit. Therefore, if small gastrin and cholecystokinin peptides from antral and intestinal mucosa are released and reach the portal venous circulation, hepatic inactivation would appear to prevent them from reaching the systemic circulation, precluding their significant contribution to gastric acid secretion and other physiologic functions.

Vasoactive intestinal peptide-producing tumor tissue fragments obtained at surgery were maintained in short-term culture. Functional cellular integrity of vasoactive intestinal peptide-producing tumor tissue was reflected by progressive protein synthesis and the ability of tumor tissue to release vasoactive intestinal peptide when stimulated by the intracellular second messengers cyclic adenosine monophosphate and calcium. Studies with verapamil and ethyleneglycol-bis (beta-aminoethylether)-N,N'-tetraacetic acid suggest that cyclic nucleotide- and ionophore A23187-mediated vasoactive intestinal peptide release are dependent, at least in part, upon the availability and transmembrane transport of extracellular calcium.

Previous studies have questioned the physiological role of gastric inhibitory peptide in inhibiting gastric acid secretion. The present study was designed to examine and compare peptone meal-stimulated gastric acid secretion in dogs after intravenous infusion of rabbit serum containing antibodies to gastric inhibitory peptide or normal rabbit serum (as control). Five dogs were prepared with gastric fistulas. Basal acid output was collected for 90 min through the gastric fistula. After 30 min of basal acid output collection, either rabbit serum containing antibodies to gastric inhibitory peptide or normal control rabbit serum (0.1 ml/kg) was infused intravenously over 1 min. After the basal acid output collection, a 10% peptone meal was infused into the stomach. Gastric acid output was measured by intragastric titration (pH 5.0) for 60 min. Peripheral venous plasma was collected for measurement of gastrin and gastric inhibitory peptide and for binding of endogenous plasma gastric inhibitory peptide by administered antibodies to gastric inhibitory peptide before and at 2, 5, 10, 15, 30, 60, 90, and 120 min after the meal. After intravenous administration of antibodies to gastric inhibitory peptide, 98% +/- 3% (SEM) of endogenous plasma gastric inhibitory peptide was bound by administered antibodies to gastric inhibitory peptide. No binding of endogenous plasma gastric inhibitory peptide was detected after infusion of normal rabbit serum. In dogs receiving intravenous antibodies to gastric inhibitory peptide, both peptone-stimulated gastric acid output and integrated gastrin release responses were increased when compared with dogs receiving normal rabbit serum. With infusion of antibodies to gastric inhibitory peptide, there was a high degree of correlation between the increase in gastric acid output and the increase in integrated gastrin response (r = 0.900, p less than 0.04) that followed the peptone meal. This study, using antibodies to bind endogenous gastric inhibitory peptide, demonstrates the capacity of circulating gastric inhibitory peptide to inhibit meal-stimulated gastric acid secretion. Furthermore, these results support the conclusion that this enterogastrone effect of gastric inhibitory peptide is due, at least in part, to inhibition of gastrin release.

Vagally denervated (Heidenhain) pouch acid outputs and serum gastrin concentrations, basal and in response to feeding, were measured in dogs before and after massive intestinal resection. Both 24-hr and postprandial Heidenhain pouch acid outputs increased (P less than 0.01) after intestinal resection. Increases in serum gastrin concentrations following feeding were greater after massive resection of the small intestine. There was an excellent correlation (r= 0.967; P less than 0.005) between increases in serum gastrin concentrations and Heidenhain pouch acid outputs after intestinal resection. These studies support and are consistent with the hypothesis that the polypeptide hormone gastrin plays a role in the production of the gastric acid hypersecretion which, in both dogs and man, frequently results from massive resection of the small intestine.

The effects of somatostatin on gastrin release and total gastrin immunoreactivity were examined under in vitro conditions in rat antral organ culture experiments. Basal antral gastrin release was inhibited by somatostatin. Total culture gastrin contents (culture medium gastrin plus extracted antral mucosal gastrin) at 6 h were reduced significantly by 10(-5) M (p less than 0.02) and 10(-4) M (P less than 0.01) somatostatin. Gastrin release into the culture media stimulated by the cholinergic agent, carbachol (10(-5) M), was suppressed by somatostatin: at 30 min and 6 h of culture 10(-8) M somatostatin inhibited carbachol-stimulated gastrin release by 66% and 54%, respectively, and 10(-5) M and 10(-4) M somatostatin completely abolished gastrin release. The rate of gastrin release stimulated by carbachol was suppressed significantly by each dose of somatostatin examined (10(-8) M to 10(-4) M). The present studies indicate that somatostatin inhibits both gastrin secretion by cultured rat antral mucosa and total antral culture gastrin contents, and demonstrate that cholinergically-mediated gastrin secretion is inhibited by somatostatin.

This overview is intended to provide perspectives drawn from the proceedings of the Ulcer-Epidemiology Symposium reported in this supplement. This meeting was designed to review the epidemiology and risk factors underlying the development of acid/peptic diseases and to highlight the natural history and therapy of these disorders. These topics served as a focus for the meeting. A second goal was to consider the topics in the context of ulcer complications resulting from use of nonsteroidal antiinflammatory drugs. Although nonsteroidal antiinflammatory drugs are well known to cause gastric damage and ulcers and to lead to complications of preexisting peptic ulcers, the frequency and severity of the clinical problems resulting from their use and the efficacy of different modalities for prevention and treatment have only recently begun to be the subjects of careful analysis.

The purpose of the present study was to examine the effects of microtubular-microfilament (MT-MF) modifying agents on gastrin release from antral mucosal cells maintained for 3 days under tissue culture conditions. Gastrin levels in the media, determined by radioimmunoassay, were monitored at hourly intervals for 6-8-hr periods. Colchicine, 1 mM, produced mild depression in media gastrin levels and completely inhibited dcAMP-theophylline-induced gastrin release. Ethyl alcohol depressed secretion of gastrin. Conversely, colchicine at 0.01 mM, significantly increased levels of gastrin. Gastrin levels were also significantly increased by tetracaine, 1 mM, and by deuterium oxide, 75% and 37.5%. Cytochalasin D had little effect on resting gastrin levels. Results of these experiments indicate response of gastrin-producing cells maintained under these conditions to a number of test agents; that the secretory responses of gastrin cells to the MT-MF modifying agents are similar to those of other endocrine cells in which concommitant changes in the MT-MF system have been studied, providing support for the proposal that this system is involved in the sequence of intracellular events which leads to gastrin secretion.

High titer antibodies to secretin were produced in rabbits by immunization with purified porcine secretin (from GIH) conjugated to bovine serum albumin in complete Freund's adjuvant. Synthetic porcine secretin (from Squibb) was radiolabeled with 125I using chloramine-T and radiosecretin was purified using talc-silica and fibrocellulose powder. Specificity of antibodies to secretin was extensively evaluated in studies examining (1) cross-reactivity with other naturally occurring hormones, (2) parellelism of serum dilutions and secretin standards, (3) quantitative recovery of secretin added to serum samples, and (4) changes in circulating immunoreactive secretin in response to intraduodenal acidification. The mean fasting serum secretin concentration in 10 dogs was 65 +/- 5 (SEM) pg per ml and in 21 healthy human volunteers it was 69 +/- 5 pg per ml. In response to intraduodenal instillation of 10 mEq of HCl, portal venous secretin concentrations increased from a mean fasting value of 52 to 450 pg per ml within 2 min; peripheral venous secretin increased from 66 to 229 pg per ml within 5 min. No significant changes in peripheral serum immunoreactive secretin concentrations were identified in dogs after a protein meal. Intravenously administered secretin in man disappeared from the circulation with mean half-life 4.06 +/- 0.82 (SEM) min.

Macrophage migration inhibition factor produced in response to purified hepatitis Bs antigen has been demonstrated in patients with and recovering from hepatitis B antigen-positive acute viral hepatitis. These results suggest that cell-mediated immunity against this antigen occurs concomitantly with the illness, and may be important in its pathogenesis. In addition, patients with chronic aggressive hepatitis, whether serologically positive or negative for hepatitis Bs antigen, were also found to have positive macrophage migration inhibition tests. This observation suggests a role for hepatitis B virus in the majority of patients with chronic aggressive hepatitis. Negative macrophage migration inhibition tests in response to the antigen were noted in acute viral hepatitis seronegative for the hepatitis B antigen, alcoholic hepatitis, normal controls, and carriers of the antigen.

Recent studies have demonstrated that somatostatin-containing cells are in close anatomic proximity to gastrin-producing cells in antral mucosa, suggesting a potential local regulatory role for somatostatin. The purpose of this study was to examine further the relationships between gastrin and somatostatin and the effects of the cholinergic agonist carbachol on content and release of gastrin and somatostatin using rat antral mucosa in tissue culture. Antral mucosa was cultured at 37 degrees C in Krebs-Henseleit buffer, pH 7.4, gassed with 95% O2-5% CO2. After 1 h, the culture medium was decanted and the tissue was boiled to extract mucosal gastrin and somatostatin. Inclusion of carbachol 2.5 X 10(-6) M in the culture medium decreased medium somatostatin from 1.91 +/- 0.28 (SEM) ng/mg tissue protein to 0.62 +/- 0.12 ng/mg (p less than 0.01), extracted mucosal somatostatin from 2.60 +/- 0.30 to 1.52 +/- 0.16 ng/mg (p less than 0.001), and percentage of somatostatin released from 42% +/- 2.6% to 27% +/- 2.2% (p less than 0.01). Carbachol also increased culture media gastrin from 14 +/- 2.5 to 27 +/- 3.0 ng/mg protein (p less than 0.01). Tissue content and release of gastrin and somatostatin were also examined during culture of rat antral mucosa in culture media containing antibodies to somatostatin in the presence and in the absence of carbachol. Incubation with somatostatin antisera, both with and without carbachol, markedly increased culture media concentrations of somatostatin, all of which was effectively bound by antibodies present in the media. Antibody binding of somatostatin was accompanied by significant increases in culture media gastrin concentrations, both in the presence and in the absence of carbachol. Results of these studies support the hypothesis that antral somatostatin exerts a local regulatory effect on gastrin release and that cholinergic stimulation of gastrin release is mediated, at least in part, through inhibition of somatostatin synthesis and release.

The role of calcium in gastrin release was investigated using rat antral organ culture. During the initial 4-h culture interval, in the absence of calcium in the culture medium, gastrin release was not different from that observed with 0.5, 1, and 2 mM calcium. However, after 6 h of culture, gastrin release with 0.5, 1, and 2 mM calcium was significantly greater than that with antral explants cultured in calcium-free media. In the presence of 1 mM calcium in the culture medium gastrin release was stimulated by dibutyryl cyclic AMP, whereas with calcium-free culture medium dibutyryl cyclic AMP was ineffective in stimulating gastrin release. Effects of ionophore A23187 on gastrin release were examined in experiments with culture medium containing no added calcium and with 2 mM calcium. The dose-response to ionophore A23187 (1.2--10 microgram/ml) with 2 mM calcium demonstrated progressive increases in culture media gastrin at 30, 60, and 120 min of culture. Maximal gastrin release occurred with 10 microgram/ml ionophore at each culture interval. Gastrin releases was not stimulated by increasing doses of ionophore when added to calcium-free organ culture media. Results of these experiments suggest that calcium is important in regulation of antral gastrin release and that dibutyryl cyclic AMP-stimulated release of antral gastrin is, at least in part, calcium-dependent. Stimulation of gastrin secretion by ionophore A23187 (in the presence of calcium) further supports the role of calcium in antral gastrin release and suggests that transport of calcium across cellular membranes is important in the coupling of secretory events in the gastrin cell.

This study was performed to examine the effects of somatostatin on antral gastrin release stimulated by postreceptor increases in adenosine cyclic nucleotide. Increases in intracellular levels of cyclic adenosine monophosphate were achieved through the use of the dibutyryl derivative of cyclic adenosine monophosphate and the phosphodiesterase inhibitor theophylline. The effects of somatostatin on basal and stimulated gastrin release were examined in rat antral organ culture experiments. Inclusion of somatostatin in the culture medium (1 X 10(-8) to 1 X 10(-4) M) resulted in significant inhibition of gastrin release at somatostatin concentrations of 1 X 10(-5) and 1 X 10(-4) M: both doses of somatostatin inhibited gastrin release by approximately 52% at 30 min and by 32% at 6 h. Gastrin release stimulated by dibutyryl cyclic adenosine monophosphate was significantly inhibited by 1 X 10(-5) and 1 X 10(-4) M somatostatin to 133% and 121% at 30 min and 77% and 98% at 6 h, respectively. Gastrin release stimulated by theophylline (1 mM) was also significantly inhibited by somatostatin in doses ranging from 1 X 10(-6) to 1 X 10(-4) M. The degree of inhibition by somatostatin of dibutyryl cyclic adenosine monophosphate- and theophylline-stimulated gastrin release declined over the duration of culture. In conclusion, these results suggest that somatostatin inhibits adenosine cyclic nucleotide-stimulated gastrin release by acting at a point distal to the formation of cyclic adenosine monophosphate.

Release of gastric inhibitory peptide into the circulation after peptone ingestion has not been demonstrated previously. In the present studies, 5 alert dogs with indwelling polyethylene portal venous catheters and gastric fistulas were studied. A meal of 10% peptone in 150 ml 0.9% NaCl, pH 7 was infused through the gastric fistula into the stomach. Gastric inhibitory peptide was measured by a specific and sensitive radioimmunoassay in sera obtained simultaneously from portal and cephalic veins before and at 1, 4, 8, 15, 30, 60, and 90 min after peptone infusion. Cephalic venous serum insulin and glucose concentrations were measured at the same time points. Mean basal portal and cephalic vein serum gastric inhibitory peptide concentrations were 136 +/- 22 and 34 +/- 10 (SEM) pg/ml, respectively. After infusion of the peptone meal, immediate increases in serum gastric inhibitory peptide levels were noted in both portal and peripheral circulation, with a peak of 597 +/- 151 pg/ml (p less than 0.02) at 8 min in portal venous serum and 323 +/- 95 pg/ml (p less than 0.05) at 15 min in cephalic venous serum. No significant increases in peripheral venous serum insulin concentration were detected throughout the entire collection period, whereas peripheral venous serum glucose levels increased slightly from a fasting level of 56 +/- 5 mg/dl to 72 +/- 5 mg/dl (p less than 0.05) at 90 min. The mean half-time of disappearance of intravenously administered gastric inhibitory peptide was found to be 7.6 +/- 1.5 (SEM) min. Results of these studies demonstrate prompt stimulation of gastric inhibitory peptide response to peptone, with peak serum gastric inhibitory peptide concentrations which are higher and occur earlier in portal than in peripheral blood. Gastric inhibitory peptide was found to have a brief half-time of disappearance, similar to that of other structurally related gastrointestinal peptides.

The value of cimetidine in treatment of duodenal ulcer and the Zollinger-Ellison syndrome appears to be well established. The drug has been enthusiastically embraced and widely used by practicing physicians. As with virtually all drugs used in the practice of medicine, cimetidine is not without its adverse effects. In some instances these effects may result from actions of cimetidine on H2-receptors on many widely distributed and diverse cells other than parietal cells, to which its potent acid-inhibiting properties are directed. Other adverse effects of cimetidine may be idiosyncratic, and, therefore, not predictable on a pharmacologic basis. In some instances the mechanisms responsible for cimetidine's adverse effects hav e yet to be defined. An assortment of abnormalities reported in patients receiving cimetidine have been suggested, but not proven, to represent adverse effects of the drug. Considering its extremely wide use, serious toxicity with cimetidine is rare. However, no potent drug, including cimetidine, used in the practice of medicine is without its adverse effects. Recognizing the present and projected extensive and probably long-term use of cimetidine, physicians and surgeons treating patients with cimetidine must maintain continued surveillance in order to detect and clarify potential undesired consequences of cimetidine administration.

The purpose of the present study was to examine the effects of the cholinergic agent carbachol on gastrin synthesis and secretion by rat antral mucosa in organ culture. In addition, the effect of atropine on basal and carbachol-stimulated gastrin release was investigated. These in vitro studies demonstrate that carbachol stimulated both gastrin secretion and synthesis in a dose-dependent manner. Maximal stimulation of gastrin synthesis and release occurred at a concentration of 1 X 10(-5) M carbachol. The rate of gastrin release stimulated by carbachol (1 X10(-5) M) was 0.79 ng-hr-1-mg-1 which was significantly greater than the control value of 0.37 ng-hr-1 (P less than 0.001). Atropine, over the dose range from 10(-7) to 10(-3) M, had no effect on basal (unstimulated) gastrin release. However, carbachol-stimulated gastrin release was inhibited progressively by inclusion of increasing concentrations of atropine in the culture media. The results of these studies indicated that the acetylcholine analogue, carbachol, is capable of directly stimulating the antral gastrin cell to significantly increase the rate of synthesis and release of gastrin. Whereas atropine, under these in vitro conditions, does not alter basal gastrin release, the muscarinic antagonist does competively inhibit carbachol-stimulated gastrin secretion.